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Kiran Sankar Maiti - One of the best experts on this subject based on the ideXlab platform.
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ultrafast vibrational coupling between c h and c o band of Cyclic Amide 2 pyrrolidinone revealed by 2dir spectroscopy
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2020Co-Authors: Kiran Sankar MaitiAbstract:Abstract Coupling between C H and C O vibrational modes play an essential role on determination of biological structure and dynamics. However, due to the weakness of the C H absorption and strong absorption of the C O vibrational band make such experiments less straightforward than those with transitions of nearly the same strength. In this communication the characteristics of the C H and C O coupling has been studied using dual frequency two dimensional infrared spectroscopy. 2-Pyrrolidinone has been used as a model molecule of biological system. The coherent and incoherent couplings between C H and C O vibrational bands have been observed. The cross peaks dynamics have been discussed and time constant of the cross peak intensity has been calculated.
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ultrafast n h vibrational dynamics of hydrogen bonded Cyclic Amide reveal by 2dir spectroscopy
Chemical Physics, 2018Co-Authors: Kiran Sankar MaitiAbstract:Abstract Hydrogen-bonding strongly influences the vibrational dynamics of the N–H stretch vibration, hence the molecular structure and dynamics. Therefore the N–H stretch vibration is an important probe to study hydrogen-bond dynamics as well as the molecular structure and dynamics, specially for the biological molecule. In this article, the dynamics and couplings of N–H stretching vibrations of biological molecules are investigated with linear infrared spectroscopy and ultrafast two-dimensional infrared (2DIR) spectroscopy with a model molecule 2-Pyrrolidinone. In solution, 2-Pyrrolidinone makes three different kinds of intermolecular hydrogen bonding, whose spectra have been collected with FTIR as well as with 2DIR spectroscopy and discussed. Inter-molecular hydrogen bond making and breaking between N–H and C O vibrational bands are discussed also.
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broadband two dimensional infrared spectroscopy of Cyclic Amide 2 pyrrolidinone
Physical Chemistry Chemical Physics, 2015Co-Authors: Kiran Sankar MaitiAbstract:In the past one-and-a-half decade there has been a significant methodological and technological development of two dimensional infrared (2DIR) spectroscopy, which unfolds many underlying physical and chemical processes of complex molecules, especially for biological molecules. Due to the extreme technical difficulties and non-uniform performance of ultrafast laser, so far, the method has been mostly applied to a small spectral region. A rather simple experimental methodology is presented here which is able to cover a broad spectral range from 1500 cm−1 to 3500 cm−1 to explore the molecular structure of Cyclic Amide, 2-Pyrrolidinone, via the time-resolved coupling of CO, CH and NH stretch vibrations. The signature of the coherent as well as incoherent coupling has been found. The Amide-I band is incoherently coupled to CH and NH stretch vibrations and acts as an acceptor mode for vibrational energy relaxation from CH and NH stretch vibrations.
Farghaly A Omar - One of the best experts on this subject based on the ideXlab platform.
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Cyclic Amide derivatives as potential prodrugs ii n hydroxymethylsuccinimide isatin esters of some nsaids as prodrugs with an improved therapeutic index
European Journal of Medicinal Chemistry, 1999Co-Authors: Nadia M Mahfouz, Farghaly A Omar, Tarek AboulfadlAbstract:Ester prodrugs of aspirin 1a, ibuprofen 1b, naproxen 1c and indomethacin 1d were synthesized using N-Hydroxymethylsuccinimide (HMSI) 3 and N-hydroxymethylisatin (HMIS) 4 as promoieties to reduce their gastrointestinal toxicity and improve bioavailability. Additionally, the kinetics of hydrolysis of the synthesized prodrugs 5a-d and 6a-d were studied at 37 degrees C in non-enzymatic simulated gastric fluid (SGF; hydrochloric acid buffer pH = 1.2); 0.02 M phosphate buffer (pH = 7.4); 80% human plasma and 10% rat liver homogenate. The results indicate higher chemical stability of the ester prodrugs in non-enzymatic SGF (t(1/2) congruent with 6.5-18.6 h) and rapid conversion to the parent drugs in 80% human plasma (t(1/2) congruent with 11.4-235 min) as well as in 10% rat liver homogenates (t(1/2) congruent with 12.0-90.0 min). As a general pattern, the HMSI esters 5a-d revealed higher chemical stability than the corresponding HMIS analogues 6a-d. The pH-rate profile of 5c and 6a indicated maximum stability of the former at pH = 1.2-8.0 and of the latter at pH = 1.2-4.0. The distribution coefficient (D(7.4)) values of the prodrugs 5a-d, 6a-d and the parent drugs 1a-d in an n-octanol/phosphate buffer (pH = 7.4) system indicated enhanced lipophilic properties of the prodrugs. Furthermore, the HMIS ester prodrugs 6a-d are more lipophilic than the corresponding HMSI derivatives 5a-d. In vivo ulcerogenicity studies using scanning electron microscopy on stomach specimens of rats treated with an oral dose for 4 d revealed that the synthesized ester prodrugs are significantly less irritating to gastric mucosa than the parent drugs. These results suggested HMSI and/or HMIS esters possess good potential as prodrugs with an improved therapeutic index for oral delivery of NSAIDs.
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Cyclic Amide derivatives as potential prodrugs synthesis and evaluation of n hydroxymethylphthalimide esters of some non steroidal anti inflammatory carboxylic acid drugs
European Journal of Medicinal Chemistry, 1998Co-Authors: Farghaly A OmarAbstract:N-l-lvdroxymethvlphthalirlide (HMPhlJ esters 5a-d o1'somc nonsteroidal anti-ini'lamnlrtorv cirugs w,cre synthesized and evaluatecl as potcntiarl prodruss with the aim of clepressing the _qastrotoxicity of thc parcnt druss by tcmporarily maskin,q thc carboxl'- lic acid tunction. The ester prodru_es were synthesized through condensation of rV -hvdroxymethvlphthalirnicle and the rnixed clrboxv- lic-carbonic:Lnhvcirirle internreciiaG or the cbrresponding aciil chloride of thc parent icicl.'iheir siructurc, were conhrmecl bv tH \l iR spectra and the puritv has been assesseci hy TLC and elernental analyscs. An HPLC rnethod hus been developed for invcstigation of the hi'droiysis kinetics in aqueous butTer solutions and in 809{,rabbit plasnra. The lipophilicity parameters lo-u P ancl log A'u,crc deter- mined and showed that the prodrugs were lbund to be rnore lipophilic (log P > 2) than the parent drugs. A considerable chcmical stability of all cornpounds (/111 = 1.1-21.9 h) has been obsened in non-enzvmatic simulated gastric fltrid (hydrochioric lcid br-rtl'er of pH l.-31, while at pH 7.-1 onlv prodrugs 5b-d are sufficiently steble (/r/. - 3-5 h). Meanwhile. rapicl conversion to the parent drugs 3a -d was observed in 807c rabbit plesrna (I,,, - I.0- I I.5 min ). Potential ulcerogenicity on rat stomach rnLlcosa of the prodrugs and the parent drugs atier oral administration lbr.l days was studiecl using a scannin_q clectron micmscope. Cross obscrvations ancl scanning electro-micrographs show,ed that the prodrugs are significantly less irritatinq rc qastric mlrcosa than the parent NSAII)s. This result suggests that N-hydroxymethylphthalimide esters rnay be r:scf ul as nonulcerogenic prodrug tirrms firr acidic NSAIDs. O lllsevier'. Paris
Ulf Göransson - One of the best experts on this subject based on the ideXlab platform.
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interlocking disulfides in circular proteins toward efficient oxidative folding of cyclotides
Antioxidants & Redox Signaling, 2011Co-Authors: Teshome Leta Aboye, Richard J Clark, David J. Craik, Robert Burman, Marta Bajona Roig, Ulf GöranssonAbstract:Cyclotides are ultrastable plant proteins characterized by the presence of a Cyclic Amide backbone and three disulfide bonds that form a cystine knot. Because of their extreme stability, there has been significant interest in developing these molecules as a drug design scaffold. For this potential to be realized, efficient methods for the synthesis and oxidative folding of cyclotides need to be developed, yet we currently have only a basic understanding of the folding mechanism and the factors influencing this process. In this study, we determine the major factors influencing oxidative folding of the different subfamilies of cyclotides. The folding of all the cyclotides examined was heavily influenced by the concentration of redox reagents, with the folding rate and final yield of the native isomer greatly enhanced by high concentrations of oxidized glutathione. Addition of hydrophobic solvents to the buffer also enhanced the folding rates and appeared to alter the folding pathway. Significant deamidation and isoaspartate formation were seen when oxidation conditions were conducive to slow folding. The identification of factors that influence the folding and degradation pathways of cyclotides will facilitate the development of folding screens and optimized conditions for producing cyclotides and grafted analogs as stable peptide-based therapeutics.
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disulfide mapping of the cyclotide kalata b1 chemical proof of the Cyclic cystine knot motif
Journal of Biological Chemistry, 2003Co-Authors: Ulf Göransson, David J. CraikAbstract:The cyclotides are a recently discovered family of plant proteins that have the fascinating structural feature of a continuous Cyclic backbone and, putatively, a knotted arrangement of their three conserved disulfide bonds. We here show definite chemical proof of the I-IV, II-V, III-VI knotted disulfide connectivity of the prototypic cyclotide kalata B1. This has been achieved by a new approach for disulfide analysis, involving partial reduction and stepwise alkylation including introduction of charges and enzymatic cleavage sites by aminoethylation of cysteines. The approach overcomes the intrinsic difficulties for disulfide mapping of cyclotides, i.e. the Cyclic Amide backbone, lack of cleavage sites between cysteines, and a low or clustered content of basic amino acids, and allowed a direct determination of the disulfide bonds in kalata B1 using analysis by mass spectrometry. The established disulfide connectivity is unequivocally shown to be cystine knotted by a topological analysis. This is the first direct chemical determination of disulfides in native cyclotides and unambiguously confirms the unique Cyclic cystine knot motif.
David J. Craik - One of the best experts on this subject based on the ideXlab platform.
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interlocking disulfides in circular proteins toward efficient oxidative folding of cyclotides
Antioxidants & Redox Signaling, 2011Co-Authors: Teshome Leta Aboye, Richard J Clark, David J. Craik, Robert Burman, Marta Bajona Roig, Ulf GöranssonAbstract:Cyclotides are ultrastable plant proteins characterized by the presence of a Cyclic Amide backbone and three disulfide bonds that form a cystine knot. Because of their extreme stability, there has been significant interest in developing these molecules as a drug design scaffold. For this potential to be realized, efficient methods for the synthesis and oxidative folding of cyclotides need to be developed, yet we currently have only a basic understanding of the folding mechanism and the factors influencing this process. In this study, we determine the major factors influencing oxidative folding of the different subfamilies of cyclotides. The folding of all the cyclotides examined was heavily influenced by the concentration of redox reagents, with the folding rate and final yield of the native isomer greatly enhanced by high concentrations of oxidized glutathione. Addition of hydrophobic solvents to the buffer also enhanced the folding rates and appeared to alter the folding pathway. Significant deamidation and isoaspartate formation were seen when oxidation conditions were conducive to slow folding. The identification of factors that influence the folding and degradation pathways of cyclotides will facilitate the development of folding screens and optimized conditions for producing cyclotides and grafted analogs as stable peptide-based therapeutics.
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disulfide mapping of the cyclotide kalata b1 chemical proof of the Cyclic cystine knot motif
Journal of Biological Chemistry, 2003Co-Authors: Ulf Göransson, David J. CraikAbstract:The cyclotides are a recently discovered family of plant proteins that have the fascinating structural feature of a continuous Cyclic backbone and, putatively, a knotted arrangement of their three conserved disulfide bonds. We here show definite chemical proof of the I-IV, II-V, III-VI knotted disulfide connectivity of the prototypic cyclotide kalata B1. This has been achieved by a new approach for disulfide analysis, involving partial reduction and stepwise alkylation including introduction of charges and enzymatic cleavage sites by aminoethylation of cysteines. The approach overcomes the intrinsic difficulties for disulfide mapping of cyclotides, i.e. the Cyclic Amide backbone, lack of cleavage sites between cysteines, and a low or clustered content of basic amino acids, and allowed a direct determination of the disulfide bonds in kalata B1 using analysis by mass spectrometry. The established disulfide connectivity is unequivocally shown to be cystine knotted by a topological analysis. This is the first direct chemical determination of disulfides in native cyclotides and unambiguously confirms the unique Cyclic cystine knot motif.
Yongjia Shang - One of the best experts on this subject based on the ideXlab platform.
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ru ii ir iii catalyzed c h bond activation annulation of Cyclic Amides with 1 3 diketone 2 diazo compounds facile access to 8h isoquinolino 1 2 b quinazolin 8 ones and phthalazino 2 3 a cinnoline 8 13 diones
ACS Omega, 2018Co-Authors: Panyuan Cai, Enshen Zhang, Taibei Fang, Chen Yang, Jian Wang, Yongjia ShangAbstract:Efficient access to 8H-isoquinolino[1,2-b]quinazolin-8-ones and phthalazino[2,3-a]cinnoline-8,13-diones through Cyclic Amide-directed Ru(II)/Ir(III)-catalyzed C–H bond activation, has been develope...
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Ru(II)/Ir(III)-Catalyzed C–H Bond Activation/Annulation of Cyclic Amides with 1,3-Diketone-2-diazo Compounds: Facile Access to 8H‑Isoquinolino[1,2‑b]quinazolin-8-ones and Phthalazino[2,3‑a]cinnoline-8,13-diones
2018Co-Authors: Panyuan Cai, Enshen Zhang, Taibei Fang, Chen Yang, Jian Wang, Yongjia ShangAbstract:Efficient access to 8H-isoquinolino[1,2-b]quinazolin-8-ones and phthalazino[2,3-a]cinnoline-8,13-diones through Cyclic Amide-directed Ru(II)/Ir(III)-catalyzed C–H bond activation, has been developed. Consecutive C–H bond activation, carbene insertion, and condensation annulation processes were realized, affording 8H-isoquinolino[1,2-b]quinazolin-8-one and phthalazino[2,3-a]cinnoline-8,13-dione derivatives in good-to-excellent yields under mild conditions, with H2O and N2 being generated as the only byproducts
