The Experts below are selected from a list of 14310 Experts worldwide ranked by ideXlab platform
Tianbao Chen - One of the best experts on this subject based on the ideXlab platform.
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characterisation of a novel peptide brevinin 1h from the Skin Secretion of amolops hainanensis and rational design of several analogues
Chemical Biology & Drug Design, 2020Co-Authors: Tianbao Chen, C. Shaw, Lei Wang, Xiaoling Chen, Xinjie Pei, Zijian Gong, Mei ZhouAbstract:As drug-resistant bacteria have become a serious health problem and have caused thousands of deaths, finding new antibiotics has become an urgent research priority. A novel antimicrobial peptide, named Brevinin-1H, was identified in the Skin Secretion of Amolops hainanensis through 'shotgun' cloning. It has broad-spectrum antimicrobial activity against tested micro-organisms and has anticancer cell activity. To improve its bioactivity and decrease its cytotoxicity, two structural analogues-Brevinin-1Ha and Brevinin-1HY-were designed based on the secondary structure of the natural peptide. Brevinin-1HY, in which tyrosine substituted Pro11 , had similar activity to the natural peptide against Gram-negative bacteria and cancer cells, but showed a dramatic increase in haemolytic activity and cytotoxicity at its minimum inhibitory concentration. Brevinin-1Ha, which transferred the Rana-box from the C-terminal to a central position, had significantly decreased haemolytic activity, but also in antimicrobial and anticancer activity. The present data suggest that increasing the proportion of α-helix structure in an AMP can increase its target micro-organism bioactivity to some extent.
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a novel antimicrobial peptide kassinatuerin 3 isolated from the Skin Secretion of the african frog kassina senegalensis
Biology, 2020Co-Authors: Mei Zhou, Tianbao Chen, C. Shaw, Hui Wang, Xiaoling Chen, Minjie Wei, Lei WangAbstract:Amphibian Skin Secretions are remarkable sources of novel bioactive peptides. Among these, antimicrobial peptides have demonstrated an outstanding efficacy in killing microorganisms via a general membranolytic mechanism, which may offer the prospect of solving specific target-driven antibiotic resistance. Here, the discovery of a novel defensive peptide is described from the Skin Secretion of the African frog, Kassina senegalensis. Named kassinatuerin-3, it was identified through a combination of "shot-gun" cloning and MS/MS fragmentation sequencing. Subsequently, a synthetic replicate was subjected to biofunctional evaluation. The results indicated that kassinatuerin-3 possessed antimicrobial activity against Gram-positive bacteria but no effect against Gram-negative bacteria. Additionally, it was active in biofilm eradication on S. aureus and MRSA and in the antiproliferation of selected cancer cell lines. Moreover, it had a very mild hemolytic effect, which demonstrated a high therapeutic index for kassinatuerin-3. Collectively, although kassinatuerin-3 did not demonstrate remarkable bioactivities compared with other natural or synthetic antimicrobial peptides (AMPs), it offered a new insight into the design of antimicrobial derivatives.
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brevinin 1ghd a novel hylarana guentheri Skin Secretion derived brevinin 1 type peptide with antimicrobial and anticancer therapeutic potential
Bioscience Reports, 2020Co-Authors: Yangyang Jiang, Mei Zhou, Tianbao Chen, C. Shaw, Xiaoling Chen, Tao Wang, Ying Zhang, Lei WangAbstract:Host-defense antimicrobial peptides (AMPs) from amphibians are usually considered as one of the most promising next-generation antibiotics because of their excellent antimicrobial properties and low cytotoxicity. In the present study, one novel Brevinin-1 type peptide, Brevinin-1GHd, was isolated and characterized from the Skin Secretion of the frog, Hylarana guentheri. Brevinin-1GHd was found to possess a wide range of antimicrobial activity through penetrating the bacterial membrane within a short time while showing low hemolysis at bactericidal concentrations, even against the resistant strains. It also inhibited and eradicated biofilms that are thought to be closely related to the rise in resistance. Meanwhile, Brevinin-1GHd exhibited wide-spectrum anti-proliferation activity toward human cancer lines. Taken together, these results indicate that Brevinin-1GHd with its excellent antimicrobial and anticancer activities is a promising candidate for a novel antibiotic agent, and study of its structure-activity relationships also provided a rational template for further research and peptide analog design.
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unravelling the Skin Secretion peptides of the gliding leaf frog agalychnis spurrelli hylidae
Biomolecules, 2019Co-Authors: Carolina Proanobolanos, Mei Zhou, Tianbao Chen, Lei Wang, Ailin Blascozuniga, Jose Rafael Almeida, Miguel Angel Llumiquinga, Miryan Rivera, C. ShawAbstract:Frog Skin Secretions contain medically-valuable molecules, which are useful for the discovery of new biopharmaceuticals. The peptide profile of the Skin Secretion of Agalychnis spurrelli has not been investigated; therefore, the structural and biological characterization of its compounds signify an inestimable opportunity to acquire new biologically-active chemical scaffolds. In this work, Skin Secretion from this amphibian was analysed by molecular cloning and tandem mass spectrometry. Although the extent of this work was not exhaustive, eleven Skin Secretion peptides belonging to five peptide families were identified. Among these, we report the occurrence of two phyllokinins, and one medusin-SP which were previously reported in other related species. In addition, eight novel peptides were identified, including four dermaseptins, DRS-SP2 to DRS-SP5, one phylloseptin-SP1, and three orphan peptides. Phylloseptin-SP1 and dermaseptins-SP2 were identified in HPLC fractions based on their molecular masses determined by MALDI-TOF MS. Among the antimicrobial peptides, dermaseptin-SP2 was the most potent, inhibiting Escherichia coli, Staphylococcus aureus, and ORSA with a minimum inhibitory concentration (MIC) of 2.68 μM, and Candida albicans with an MIC of 10.71 μM, without haemolytic effects. The peptides described in this study represent but a superficial glance at the considerable structural diversity of bioactive peptides produced in the Skin Secretion of A. spurrelli.
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A Novel Kunitzin-Like Trypsin Inhibitor Isolated from Defensive Skin Secretion of Odorrana versabilis.
Biomolecules, 2019Co-Authors: Yanjing Dong, Mei Zhou, Lei Wang, Daning Shi, Yuan Ying, Xiaoling Chen, Tianbao ChenAbstract:Protease inhibitors that were identified from amphibian Skin Secretions with low molecular weights and potent inhibitory activity were thought to be potential candidates for novel peptide drugs. Here, a novel peptide with trypsin inhibitory activity was found in the Skin Secretion of the Chinese bamboo leaf odorous frog, Odorrana versabilis. Based on the sequence alignments of sequencing results, the novel peptide (ALKYPFRCKAAFC) was named as Kunitzin-OV. The synthetic replicate of Kunitzin-OV was subjected to a series of functional assays, and it exhibited a trypsin inhibitory activity with a Ki value of 3.042 µM, whereas, when Lys-9 at P1 position was substituted by Phe, trypsin inhibitory activity was undetected and the chymotrypsin inhibitory activity was optimized with a Ki value of 2.874 µM. However, its protease-binding loop was catabolized by trypsin during the trypsin cleavage test. In conclusion, Kunizin-OV is a novel peptide with trypsin inhibitory activity as a member of kunitzins, which is a non-typical Kunitz-like trypsin inhibitor with a highly conserved reactive site (K-A) and quite a short sequence.
C. Shaw - One of the best experts on this subject based on the ideXlab platform.
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characterisation of a novel peptide brevinin 1h from the Skin Secretion of amolops hainanensis and rational design of several analogues
Chemical Biology & Drug Design, 2020Co-Authors: Tianbao Chen, C. Shaw, Lei Wang, Xiaoling Chen, Xinjie Pei, Zijian Gong, Mei ZhouAbstract:As drug-resistant bacteria have become a serious health problem and have caused thousands of deaths, finding new antibiotics has become an urgent research priority. A novel antimicrobial peptide, named Brevinin-1H, was identified in the Skin Secretion of Amolops hainanensis through 'shotgun' cloning. It has broad-spectrum antimicrobial activity against tested micro-organisms and has anticancer cell activity. To improve its bioactivity and decrease its cytotoxicity, two structural analogues-Brevinin-1Ha and Brevinin-1HY-were designed based on the secondary structure of the natural peptide. Brevinin-1HY, in which tyrosine substituted Pro11 , had similar activity to the natural peptide against Gram-negative bacteria and cancer cells, but showed a dramatic increase in haemolytic activity and cytotoxicity at its minimum inhibitory concentration. Brevinin-1Ha, which transferred the Rana-box from the C-terminal to a central position, had significantly decreased haemolytic activity, but also in antimicrobial and anticancer activity. The present data suggest that increasing the proportion of α-helix structure in an AMP can increase its target micro-organism bioactivity to some extent.
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a novel antimicrobial peptide kassinatuerin 3 isolated from the Skin Secretion of the african frog kassina senegalensis
Biology, 2020Co-Authors: Mei Zhou, Tianbao Chen, C. Shaw, Hui Wang, Xiaoling Chen, Minjie Wei, Lei WangAbstract:Amphibian Skin Secretions are remarkable sources of novel bioactive peptides. Among these, antimicrobial peptides have demonstrated an outstanding efficacy in killing microorganisms via a general membranolytic mechanism, which may offer the prospect of solving specific target-driven antibiotic resistance. Here, the discovery of a novel defensive peptide is described from the Skin Secretion of the African frog, Kassina senegalensis. Named kassinatuerin-3, it was identified through a combination of "shot-gun" cloning and MS/MS fragmentation sequencing. Subsequently, a synthetic replicate was subjected to biofunctional evaluation. The results indicated that kassinatuerin-3 possessed antimicrobial activity against Gram-positive bacteria but no effect against Gram-negative bacteria. Additionally, it was active in biofilm eradication on S. aureus and MRSA and in the antiproliferation of selected cancer cell lines. Moreover, it had a very mild hemolytic effect, which demonstrated a high therapeutic index for kassinatuerin-3. Collectively, although kassinatuerin-3 did not demonstrate remarkable bioactivities compared with other natural or synthetic antimicrobial peptides (AMPs), it offered a new insight into the design of antimicrobial derivatives.
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brevinin 1ghd a novel hylarana guentheri Skin Secretion derived brevinin 1 type peptide with antimicrobial and anticancer therapeutic potential
Bioscience Reports, 2020Co-Authors: Yangyang Jiang, Mei Zhou, Tianbao Chen, C. Shaw, Xiaoling Chen, Tao Wang, Ying Zhang, Lei WangAbstract:Host-defense antimicrobial peptides (AMPs) from amphibians are usually considered as one of the most promising next-generation antibiotics because of their excellent antimicrobial properties and low cytotoxicity. In the present study, one novel Brevinin-1 type peptide, Brevinin-1GHd, was isolated and characterized from the Skin Secretion of the frog, Hylarana guentheri. Brevinin-1GHd was found to possess a wide range of antimicrobial activity through penetrating the bacterial membrane within a short time while showing low hemolysis at bactericidal concentrations, even against the resistant strains. It also inhibited and eradicated biofilms that are thought to be closely related to the rise in resistance. Meanwhile, Brevinin-1GHd exhibited wide-spectrum anti-proliferation activity toward human cancer lines. Taken together, these results indicate that Brevinin-1GHd with its excellent antimicrobial and anticancer activities is a promising candidate for a novel antibiotic agent, and study of its structure-activity relationships also provided a rational template for further research and peptide analog design.
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unravelling the Skin Secretion peptides of the gliding leaf frog agalychnis spurrelli hylidae
Biomolecules, 2019Co-Authors: Carolina Proanobolanos, Mei Zhou, Tianbao Chen, Lei Wang, Ailin Blascozuniga, Jose Rafael Almeida, Miguel Angel Llumiquinga, Miryan Rivera, C. ShawAbstract:Frog Skin Secretions contain medically-valuable molecules, which are useful for the discovery of new biopharmaceuticals. The peptide profile of the Skin Secretion of Agalychnis spurrelli has not been investigated; therefore, the structural and biological characterization of its compounds signify an inestimable opportunity to acquire new biologically-active chemical scaffolds. In this work, Skin Secretion from this amphibian was analysed by molecular cloning and tandem mass spectrometry. Although the extent of this work was not exhaustive, eleven Skin Secretion peptides belonging to five peptide families were identified. Among these, we report the occurrence of two phyllokinins, and one medusin-SP which were previously reported in other related species. In addition, eight novel peptides were identified, including four dermaseptins, DRS-SP2 to DRS-SP5, one phylloseptin-SP1, and three orphan peptides. Phylloseptin-SP1 and dermaseptins-SP2 were identified in HPLC fractions based on their molecular masses determined by MALDI-TOF MS. Among the antimicrobial peptides, dermaseptin-SP2 was the most potent, inhibiting Escherichia coli, Staphylococcus aureus, and ORSA with a minimum inhibitory concentration (MIC) of 2.68 μM, and Candida albicans with an MIC of 10.71 μM, without haemolytic effects. The peptides described in this study represent but a superficial glance at the considerable structural diversity of bioactive peptides produced in the Skin Secretion of A. spurrelli.
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lfb a novel antimicrobial brevinin like peptide from the Skin Secretion of the fujian large headed frog limnonectes fujianensi
Biomolecules, 2019Co-Authors: Tianbao Chen, C. Shaw, Peng Lyu, Shuping Xie, Haixin Qin, Hang Fai KwokAbstract:Amphibians are a natural source of abundant antimicrobial peptides and thus have been widely investigated for isolation of such biomolecules. Many new antimicrobial peptide families have been discovered from amphibians. In this study, a novel antimicrobial peptide named Limnonectes fujianensis Brevinvin (LFB) has been identified in the Skin Secretion from the Fujian large headed frog, Limnonectes fujianensis. The cDNA sequence was cloned from a Skin Secretion library and the predicted mature peptide was identified through MS/MS fragmentation sequencing of reverse phase HPLC fractions on the same sample. LFB was predicted to be an amphipathic, hydrophobic, alpha helical, and beta turn peptide that inserts into a lipid bilayer in order to kill the cells. In antimicrobial assays, a synthetic replicate of this novel antimicrobial peptide demonstrated significant activity against the Gram-positive bacterium Staphylococcus aureus, the Gram-negative bacterium Escherichia coli and the yeast, Candida albicans. This novel peptide was highly potent (MIC 4.88 uM) against Gram-negative bacterium, and also has the ability to inhibit the growth of human cancer cell lines with IC50 values ranging from 18.9 μM down to 2.0 μM. These findings help to enrich our understanding of Brevinin-like peptides. Moreover, the data presented here validate frog Secretion as a source of potential novel antimicrobial peptides, that also exhibit anti-tumor properties, that could be useful for the treatment of cancer.
Mei Zhou - One of the best experts on this subject based on the ideXlab platform.
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characterisation of a novel peptide brevinin 1h from the Skin Secretion of amolops hainanensis and rational design of several analogues
Chemical Biology & Drug Design, 2020Co-Authors: Tianbao Chen, C. Shaw, Lei Wang, Xiaoling Chen, Xinjie Pei, Zijian Gong, Mei ZhouAbstract:As drug-resistant bacteria have become a serious health problem and have caused thousands of deaths, finding new antibiotics has become an urgent research priority. A novel antimicrobial peptide, named Brevinin-1H, was identified in the Skin Secretion of Amolops hainanensis through 'shotgun' cloning. It has broad-spectrum antimicrobial activity against tested micro-organisms and has anticancer cell activity. To improve its bioactivity and decrease its cytotoxicity, two structural analogues-Brevinin-1Ha and Brevinin-1HY-were designed based on the secondary structure of the natural peptide. Brevinin-1HY, in which tyrosine substituted Pro11 , had similar activity to the natural peptide against Gram-negative bacteria and cancer cells, but showed a dramatic increase in haemolytic activity and cytotoxicity at its minimum inhibitory concentration. Brevinin-1Ha, which transferred the Rana-box from the C-terminal to a central position, had significantly decreased haemolytic activity, but also in antimicrobial and anticancer activity. The present data suggest that increasing the proportion of α-helix structure in an AMP can increase its target micro-organism bioactivity to some extent.
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Enhanced Antimicrobial Activity of N-Terminal Derivatives of a Novel Brevinin-1 Peptide from The Skin Secretion of Odorrana schmackeri.
Toxins, 2020Co-Authors: Xiaowei Zhou, Yitian Gao, Mei Zhou, Yue Liu, Yuanxing Wang, Qiang Xia, Ruimin Zhong, Christopher ShawAbstract:Antimicrobial peptides (AMPs) are promising therapeutic alternatives compared to conventional antibiotics for the treatment of drug-resistant bacterial infections. However, the application of the overwhelming majority of AMPs is limited because of the high toxicity and high manufacturing costs. Amphibian Skin Secretion has been proven to be a promising source for the discovery and development of novel AMPs. Herein, we discovered a novel AMP from the Skin Secretion of Odorrana schmackeri, and designed the analogues by altering the key factors, including conformation, net charge and amphipathicity, to generate short AMPs with enhanced therapeutic efficacy. All the peptides were chemically synthesised, followed by evaluating their biological activity, stability and cytotoxicity. OSd, OSe and OSf exhibited broad-spectrum antibacterial effects, especially OSf, which presented the highest therapeutic index for the tested bacteria. Moreover, these peptides displayed good stability. The results from scanning electron microscopy and transmission electron microscopy studies, indicated that brevinin-OS, OSd, OSe and OSf possessed rapid bactericidal ability by disturbing membrane permeability and causing the release of cytoplasmic contents. In addition, OSd, OSe and OSf dramatically decreased the mortality of waxworms acutely infected with MRSA. Taken together, these data suggested that a balance between positive charge, degrees of α-helicity and hydrophobicity, is necessary for maintaining antimicrobial activity, and these data successfully contributed to the design of short AMPs with significant bactericidal activity and cell selectivity.
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a novel antimicrobial peptide kassinatuerin 3 isolated from the Skin Secretion of the african frog kassina senegalensis
Biology, 2020Co-Authors: Mei Zhou, Tianbao Chen, C. Shaw, Hui Wang, Xiaoling Chen, Minjie Wei, Lei WangAbstract:Amphibian Skin Secretions are remarkable sources of novel bioactive peptides. Among these, antimicrobial peptides have demonstrated an outstanding efficacy in killing microorganisms via a general membranolytic mechanism, which may offer the prospect of solving specific target-driven antibiotic resistance. Here, the discovery of a novel defensive peptide is described from the Skin Secretion of the African frog, Kassina senegalensis. Named kassinatuerin-3, it was identified through a combination of "shot-gun" cloning and MS/MS fragmentation sequencing. Subsequently, a synthetic replicate was subjected to biofunctional evaluation. The results indicated that kassinatuerin-3 possessed antimicrobial activity against Gram-positive bacteria but no effect against Gram-negative bacteria. Additionally, it was active in biofilm eradication on S. aureus and MRSA and in the antiproliferation of selected cancer cell lines. Moreover, it had a very mild hemolytic effect, which demonstrated a high therapeutic index for kassinatuerin-3. Collectively, although kassinatuerin-3 did not demonstrate remarkable bioactivities compared with other natural or synthetic antimicrobial peptides (AMPs), it offered a new insight into the design of antimicrobial derivatives.
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brevinin 1ghd a novel hylarana guentheri Skin Secretion derived brevinin 1 type peptide with antimicrobial and anticancer therapeutic potential
Bioscience Reports, 2020Co-Authors: Yangyang Jiang, Mei Zhou, Tianbao Chen, C. Shaw, Xiaoling Chen, Tao Wang, Ying Zhang, Lei WangAbstract:Host-defense antimicrobial peptides (AMPs) from amphibians are usually considered as one of the most promising next-generation antibiotics because of their excellent antimicrobial properties and low cytotoxicity. In the present study, one novel Brevinin-1 type peptide, Brevinin-1GHd, was isolated and characterized from the Skin Secretion of the frog, Hylarana guentheri. Brevinin-1GHd was found to possess a wide range of antimicrobial activity through penetrating the bacterial membrane within a short time while showing low hemolysis at bactericidal concentrations, even against the resistant strains. It also inhibited and eradicated biofilms that are thought to be closely related to the rise in resistance. Meanwhile, Brevinin-1GHd exhibited wide-spectrum anti-proliferation activity toward human cancer lines. Taken together, these results indicate that Brevinin-1GHd with its excellent antimicrobial and anticancer activities is a promising candidate for a novel antibiotic agent, and study of its structure-activity relationships also provided a rational template for further research and peptide analog design.
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unravelling the Skin Secretion peptides of the gliding leaf frog agalychnis spurrelli hylidae
Biomolecules, 2019Co-Authors: Carolina Proanobolanos, Mei Zhou, Tianbao Chen, Lei Wang, Ailin Blascozuniga, Jose Rafael Almeida, Miguel Angel Llumiquinga, Miryan Rivera, C. ShawAbstract:Frog Skin Secretions contain medically-valuable molecules, which are useful for the discovery of new biopharmaceuticals. The peptide profile of the Skin Secretion of Agalychnis spurrelli has not been investigated; therefore, the structural and biological characterization of its compounds signify an inestimable opportunity to acquire new biologically-active chemical scaffolds. In this work, Skin Secretion from this amphibian was analysed by molecular cloning and tandem mass spectrometry. Although the extent of this work was not exhaustive, eleven Skin Secretion peptides belonging to five peptide families were identified. Among these, we report the occurrence of two phyllokinins, and one medusin-SP which were previously reported in other related species. In addition, eight novel peptides were identified, including four dermaseptins, DRS-SP2 to DRS-SP5, one phylloseptin-SP1, and three orphan peptides. Phylloseptin-SP1 and dermaseptins-SP2 were identified in HPLC fractions based on their molecular masses determined by MALDI-TOF MS. Among the antimicrobial peptides, dermaseptin-SP2 was the most potent, inhibiting Escherichia coli, Staphylococcus aureus, and ORSA with a minimum inhibitory concentration (MIC) of 2.68 μM, and Candida albicans with an MIC of 10.71 μM, without haemolytic effects. The peptides described in this study represent but a superficial glance at the considerable structural diversity of bioactive peptides produced in the Skin Secretion of A. spurrelli.
Lei Wang - One of the best experts on this subject based on the ideXlab platform.
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characterisation of a novel peptide brevinin 1h from the Skin Secretion of amolops hainanensis and rational design of several analogues
Chemical Biology & Drug Design, 2020Co-Authors: Tianbao Chen, C. Shaw, Lei Wang, Xiaoling Chen, Xinjie Pei, Zijian Gong, Mei ZhouAbstract:As drug-resistant bacteria have become a serious health problem and have caused thousands of deaths, finding new antibiotics has become an urgent research priority. A novel antimicrobial peptide, named Brevinin-1H, was identified in the Skin Secretion of Amolops hainanensis through 'shotgun' cloning. It has broad-spectrum antimicrobial activity against tested micro-organisms and has anticancer cell activity. To improve its bioactivity and decrease its cytotoxicity, two structural analogues-Brevinin-1Ha and Brevinin-1HY-were designed based on the secondary structure of the natural peptide. Brevinin-1HY, in which tyrosine substituted Pro11 , had similar activity to the natural peptide against Gram-negative bacteria and cancer cells, but showed a dramatic increase in haemolytic activity and cytotoxicity at its minimum inhibitory concentration. Brevinin-1Ha, which transferred the Rana-box from the C-terminal to a central position, had significantly decreased haemolytic activity, but also in antimicrobial and anticancer activity. The present data suggest that increasing the proportion of α-helix structure in an AMP can increase its target micro-organism bioactivity to some extent.
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a novel antimicrobial peptide kassinatuerin 3 isolated from the Skin Secretion of the african frog kassina senegalensis
Biology, 2020Co-Authors: Mei Zhou, Tianbao Chen, C. Shaw, Hui Wang, Xiaoling Chen, Minjie Wei, Lei WangAbstract:Amphibian Skin Secretions are remarkable sources of novel bioactive peptides. Among these, antimicrobial peptides have demonstrated an outstanding efficacy in killing microorganisms via a general membranolytic mechanism, which may offer the prospect of solving specific target-driven antibiotic resistance. Here, the discovery of a novel defensive peptide is described from the Skin Secretion of the African frog, Kassina senegalensis. Named kassinatuerin-3, it was identified through a combination of "shot-gun" cloning and MS/MS fragmentation sequencing. Subsequently, a synthetic replicate was subjected to biofunctional evaluation. The results indicated that kassinatuerin-3 possessed antimicrobial activity against Gram-positive bacteria but no effect against Gram-negative bacteria. Additionally, it was active in biofilm eradication on S. aureus and MRSA and in the antiproliferation of selected cancer cell lines. Moreover, it had a very mild hemolytic effect, which demonstrated a high therapeutic index for kassinatuerin-3. Collectively, although kassinatuerin-3 did not demonstrate remarkable bioactivities compared with other natural or synthetic antimicrobial peptides (AMPs), it offered a new insight into the design of antimicrobial derivatives.
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brevinin 1ghd a novel hylarana guentheri Skin Secretion derived brevinin 1 type peptide with antimicrobial and anticancer therapeutic potential
Bioscience Reports, 2020Co-Authors: Yangyang Jiang, Mei Zhou, Tianbao Chen, C. Shaw, Xiaoling Chen, Tao Wang, Ying Zhang, Lei WangAbstract:Host-defense antimicrobial peptides (AMPs) from amphibians are usually considered as one of the most promising next-generation antibiotics because of their excellent antimicrobial properties and low cytotoxicity. In the present study, one novel Brevinin-1 type peptide, Brevinin-1GHd, was isolated and characterized from the Skin Secretion of the frog, Hylarana guentheri. Brevinin-1GHd was found to possess a wide range of antimicrobial activity through penetrating the bacterial membrane within a short time while showing low hemolysis at bactericidal concentrations, even against the resistant strains. It also inhibited and eradicated biofilms that are thought to be closely related to the rise in resistance. Meanwhile, Brevinin-1GHd exhibited wide-spectrum anti-proliferation activity toward human cancer lines. Taken together, these results indicate that Brevinin-1GHd with its excellent antimicrobial and anticancer activities is a promising candidate for a novel antibiotic agent, and study of its structure-activity relationships also provided a rational template for further research and peptide analog design.
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unravelling the Skin Secretion peptides of the gliding leaf frog agalychnis spurrelli hylidae
Biomolecules, 2019Co-Authors: Carolina Proanobolanos, Mei Zhou, Tianbao Chen, Lei Wang, Ailin Blascozuniga, Jose Rafael Almeida, Miguel Angel Llumiquinga, Miryan Rivera, C. ShawAbstract:Frog Skin Secretions contain medically-valuable molecules, which are useful for the discovery of new biopharmaceuticals. The peptide profile of the Skin Secretion of Agalychnis spurrelli has not been investigated; therefore, the structural and biological characterization of its compounds signify an inestimable opportunity to acquire new biologically-active chemical scaffolds. In this work, Skin Secretion from this amphibian was analysed by molecular cloning and tandem mass spectrometry. Although the extent of this work was not exhaustive, eleven Skin Secretion peptides belonging to five peptide families were identified. Among these, we report the occurrence of two phyllokinins, and one medusin-SP which were previously reported in other related species. In addition, eight novel peptides were identified, including four dermaseptins, DRS-SP2 to DRS-SP5, one phylloseptin-SP1, and three orphan peptides. Phylloseptin-SP1 and dermaseptins-SP2 were identified in HPLC fractions based on their molecular masses determined by MALDI-TOF MS. Among the antimicrobial peptides, dermaseptin-SP2 was the most potent, inhibiting Escherichia coli, Staphylococcus aureus, and ORSA with a minimum inhibitory concentration (MIC) of 2.68 μM, and Candida albicans with an MIC of 10.71 μM, without haemolytic effects. The peptides described in this study represent but a superficial glance at the considerable structural diversity of bioactive peptides produced in the Skin Secretion of A. spurrelli.
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A Novel Kunitzin-Like Trypsin Inhibitor Isolated from Defensive Skin Secretion of Odorrana versabilis.
Biomolecules, 2019Co-Authors: Yanjing Dong, Mei Zhou, Lei Wang, Daning Shi, Yuan Ying, Xiaoling Chen, Tianbao ChenAbstract:Protease inhibitors that were identified from amphibian Skin Secretions with low molecular weights and potent inhibitory activity were thought to be potential candidates for novel peptide drugs. Here, a novel peptide with trypsin inhibitory activity was found in the Skin Secretion of the Chinese bamboo leaf odorous frog, Odorrana versabilis. Based on the sequence alignments of sequencing results, the novel peptide (ALKYPFRCKAAFC) was named as Kunitzin-OV. The synthetic replicate of Kunitzin-OV was subjected to a series of functional assays, and it exhibited a trypsin inhibitory activity with a Ki value of 3.042 µM, whereas, when Lys-9 at P1 position was substituted by Phe, trypsin inhibitory activity was undetected and the chymotrypsin inhibitory activity was optimized with a Ki value of 2.874 µM. However, its protease-binding loop was catabolized by trypsin during the trypsin cleavage test. In conclusion, Kunizin-OV is a novel peptide with trypsin inhibitory activity as a member of kunitzins, which is a non-typical Kunitz-like trypsin inhibitor with a highly conserved reactive site (K-A) and quite a short sequence.
Christopher Shaw - One of the best experts on this subject based on the ideXlab platform.
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Enhanced Antimicrobial Activity of N-Terminal Derivatives of a Novel Brevinin-1 Peptide from The Skin Secretion of Odorrana schmackeri.
Toxins, 2020Co-Authors: Xiaowei Zhou, Yitian Gao, Mei Zhou, Yue Liu, Yuanxing Wang, Qiang Xia, Ruimin Zhong, Christopher ShawAbstract:Antimicrobial peptides (AMPs) are promising therapeutic alternatives compared to conventional antibiotics for the treatment of drug-resistant bacterial infections. However, the application of the overwhelming majority of AMPs is limited because of the high toxicity and high manufacturing costs. Amphibian Skin Secretion has been proven to be a promising source for the discovery and development of novel AMPs. Herein, we discovered a novel AMP from the Skin Secretion of Odorrana schmackeri, and designed the analogues by altering the key factors, including conformation, net charge and amphipathicity, to generate short AMPs with enhanced therapeutic efficacy. All the peptides were chemically synthesised, followed by evaluating their biological activity, stability and cytotoxicity. OSd, OSe and OSf exhibited broad-spectrum antibacterial effects, especially OSf, which presented the highest therapeutic index for the tested bacteria. Moreover, these peptides displayed good stability. The results from scanning electron microscopy and transmission electron microscopy studies, indicated that brevinin-OS, OSd, OSe and OSf possessed rapid bactericidal ability by disturbing membrane permeability and causing the release of cytoplasmic contents. In addition, OSd, OSe and OSf dramatically decreased the mortality of waxworms acutely infected with MRSA. Taken together, these data suggested that a balance between positive charge, degrees of α-helicity and hydrophobicity, is necessary for maintaining antimicrobial activity, and these data successfully contributed to the design of short AMPs with significant bactericidal activity and cell selectivity.
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Skin Secretion transcriptome remains in chromatographic fractions suitable for molecular cloning.
Analytical biochemistry, 2018Co-Authors: Carolina Proaño-bolaños, Mei Zhou, Tianbao Chen, Christopher ShawAbstract:Abstract Traditional sources of mRNA for molecular cloning on amphibian Skin Secretion studies have been the frog's Skin and Skin Secretions. Here, we demonstrate that mRNA isolated from chromatographic fractions of Skin Secretions is amenable for molecular cloning assays. We identified precursor sequences of the Arg0, Trp5, Leu8-bradykinin and six antimicrobial peptides of Pelophylax esculentus (Ranidae). These results show that both transcriptomic and peptidomic analyses can be performed with a single sample reducing in half the amount of starting Skin Secretion required. This is a significant advantage when working with endangered or very rare amphibian species, where minimal samples are available.
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Identification of a Novel Vasodilatory Octapeptide from the Skin Secretion of the African Hyperoliid Frog, Kassina senegalensis
Molecules (Basel Switzerland), 2017Co-Authors: Hui Wang, Mei Zhou, Tianbao Chen, Christopher Shaw, Lei WangAbstract:The defensive Skin Secretions of amphibians continue to be an excellent source of novel biologically-active peptides. Here we report the identification and pharmacological activity of a novel C-terminally amided myotropic octapeptide from the Skin Secretion of the African hyperoliid frog, Kassina senegalensis. The 8-amino acid peptide has the following primary structure: WMSLGWSL-amide and has a molecular mass of 978 Da. The primary structure and organisation of the biosynthetic precursor of WL-8 amide was successfully deduced from cloned Skin Secretion-derived cDNA. The open-reading frame encoded a single copy of WL-8, located at the C-terminus. Synthetic WL-8 amide was found to cause relaxation of rat tail artery smooth muscle with an EC50 of 25.98 nM. This peptide is unique in terms of its primary structure and is unlike any other peptide previously isolated from an amphibian source which has been archived in the NCBI database. WL-8 amide thus represents the prototype of a novel family of myotropic peptide from amphibian defensive Skin Secretions.
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Identification and bioactivity evaluation of a novel bradykinin inhibitory peptide from the Skin Secretion of Chinese large odorous frog, Odorrana livida
Journal of Peptide Science, 2016Co-Authors: Kundi Yang, Mei Zhou, Tianbao Chen, Lei Wang, Christopher ShawAbstract:A novel peptide was isolated from the Skin Secretion of Chinese large odorous frog, Odorrana livida, and was named as Rana-BI. The cDNA sequencing was obtained by 'shotgun' cloning. The amino acid sequence of the mature peptide was identified as Gly-Leu-Leu-Ser-Gly-Lys-Ser-Val-Lys-Gly-Ser-Ile-OH by automated Edman degradation, and the molecular weight of the peptide was confirmed to be 1144.68 Da by MALDI-TOF and liquid chromatography/MS. Subsequently, the bioactivity of synthetic peptide was evaluated by smooth muscle assay using isolated rat bladder preparation. It was demonstrated that Rana-BI inhibited the contraction of rat bladder induced by bradykinin. Comparing with other peptides by searching from database, the primary structure of Rana-BI showed high similarity with that of an antimicrobial peptide of Rana family (12/12 residues). These data revealed a novel biological function of this peptide.
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Hylaranins: prototypes of a new class of amphibian antimicrobial peptide from the Skin Secretion of the oriental broad-folded frog, Hylarana latouchii
Amino acids, 2013Co-Authors: Yan Lin, Mei Zhou, Tianbao Chen, Lei Wang, Peng Lyu, Suhua Guo, Christopher ShawAbstract:Amphibian Skin Secretions contain a broad spectrum of biologically active compounds, particularly antimicrobial peptides, which are considered to constitute a first line of defence against bacterial infection. Here we describe the identification of two prototype peptides representing a novel structural class of antimicrobial peptide from the Skin Secretion of the oriental broad-folded frog, Hylarana latouchii. Named hylaranin-L1 (GVLSAFKNALPGIMKIIVamide) and hylaranin-L2 (GVLSVIKNALPGIMRFIAamide), both peptides consist of 18 amino acid residues, are C-terminally amidated and are of unique primary structures. Their primary structures were initially deduced by MS/MS fragmentation sequencing from reverse-phase HPLC fractions of Skin Secretion that demonstrated antimicrobial activity. Subsequently, their precursor-encoding cDNAs were cloned from a Skin Secretion-derived cDNA library and their primary structures were confirmed unequivocally. Synthetic replicates of both peptides exhibited broad-spectrum antimicrobial activity with mean inhibitory concentrations (MICs) of 34 μM against Gram-negative Escherichia coli, 4.3 μM against Gram-positive Staphylococcus aureus and 4–9 μM against the yeast, Candida albicans. Both peptides exhibited little haemolytic activity (
