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Heikki Vapaatalo - One of the best experts on this subject based on the ideXlab platform.
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Effects of milk casein derived Tripeptides on endothelial enzymes in vitro; a study with synthetic Tripeptides.
Drug Research, 2012Co-Authors: Aino Siltari, Riitta Korpela, Anne S. Kivimäki, Pauliina I. Ehlers, Heikki VapaataloAbstract:In the fermentation of milk by certain lactic acid bacteria, casein is degraded into bioactive Tripeptides shown to lower blood pressure in experimental animal models and in mildly hypertensive humans. This effect is suggested to result mainly in inhibition of angiotensin converting enzyme 1 (ACE-1). Due to the complexity of renin-angiotensin system (RAS), several other enzymes than ACE-1 can participate in the production of vasoactive components. Therefore, in the present study we investigated effects of Tripeptides isoleucine-proline-proline (IPP), valine-proline-proline (VPP) and leucine-proline-proline (LPP) on some endothelial enzymes that are important in RAS or otherwise have a role in the endothelial function. The enzymes investigated were renin, chymase, neutral endopeptidase (NEP), prolyl oligopeptidase (POP), cathepsin G, endothelin converting enzyme 1 (ECE-1), and cyclooxygenase 1 and 2 (COX -1 and COX-2). The Tripeptides inhibited prolyl oligopeptidase (POP) dose-dependently. IPP was the most potent inhibitor (IC 50 486±95 µM). Contrary, cathepsin G was activated by IPP, VPP and LPP as well as the amino acids proline and isoleucine. The other investigated enzymes were not affected. Inhibition of POP and activation of cathepsin G do not explain the blood pressure lowering effects of the Tripeptides. Thus the inhibition of ACE-1 remains the most plausible mechanism of the antihypertensive effects of the Tripeptides.
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cardiovascular activity of milk casein derived Tripeptides and plant sterols in spontaneously hypertensive rats
Journal of Physiology and Pharmacology, 2009Co-Authors: Pauliina Jakala, E Pere, Risto Lehtinen, Anu M Turpeinen, Riitta Korpela, Heikki VapaataloAbstract:: The effect of chronic treatment with fermented milk products containing bioactive Tripeptides and plant sterols on blood pressure and vascular function was investigated in spontaneously hypertensive rats (SHR). Six-weeks old male SHR (n=36) were randomized into 4 groups by body weight and blood pressure to receive either Lactobacillus helveticus fermented standard milk product (containing Tripeptides Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro), test product with enzymatically produced Tripeptides without or with plant sterols or control product without the active constituents for 8 weeks. Systolic blood pressure (SBP) was measured weekly using the tail-cuff method. Thoracic aorta and mesenteric artery were excised for vascular response measurements. At the end, SBP values vs. control product group were: standard product group -14 mmHg (P<0.05), test product group -12 mmHg and test product +sterols group -7 mmHg. The average daily tripeptide dose was 2.8-5.2 mg/kg. Total serum cholesterol in the test product +sterols group tended to be lower than in the test product group (P=0.10) whereas serum plant sterol (campesterol, sitosterol) concentrations were higher (P<0.001). In conclusion, bioactive tripeptide-containing milk products attenuated the blood pressure development in SHR. The plant sterols did not improve this effect. Vascular responses did not markedly differ between the groups, except that endothelium-derived hyperpolarizing factor (EDHF) -related aortic relaxation was demonstrated in the test product +sterols group.
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casein derived bioactive Tripeptides ile pro pro and val pro pro attenuate the development of hypertension and improve endothelial function in salt loaded goto kakizaki rats
Journal of Functional Foods, 2009Co-Authors: Pauliina Jakala, Anu M Turpeinen, Riitta Korpela, Anne Hakala, Heikki VapaataloAbstract:Abstract Increased blood pressure and plasma cholesterol concentration are the major risk factors for cardiovascular diseases. We have previously shown that fermented milk products containing casein-derived bioactive Tripeptides, isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) partly inhibit the blood pressure increase in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of bioactive tripeptide-containing fermented milk products (with or without plant sterols) on blood pressure and vascular function in salt-loaded type 2 diabetic Goto–Kakizaki (GK) rats after 8 weeks’ treatment. The development of blood pressure was attenuated in the groups receiving tripeptide-containing products (−10 to −12 mmHg vs. the control product group, P
Birger Brodin - One of the best experts on this subject based on the ideXlab platform.
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a quantitative structure activity relationship for translocation of Tripeptides via the human proton coupled peptide transporter hpept1 slc15a1
Aaps Journal, 2010Co-Authors: Diana Hojmark Omkvist, Simon Birkso Larsen, Carsten Uhd Nielsen, Bente Steffansen, Lars Olsen, Flemming Jorgensen, Birger BrodinAbstract:The human intestinal proton-coupled peptide transporter, hPEPT1 (SLC15A1), has been identified as an absorptive transporter for both drug substances and prodrugs. An understanding of the prerequisites for transport has so far been obtained from models based on competition experiments. These models have limited value for predicting substrate translocation via hPEPT1. The aim of the present study was to investigate the requirements for translocation via hPEPT1. A set of 55 Tripeptides was selected from a principal component analysis based on VolSurf descriptors using a statistical design. The majority of theses Tripeptides have not previously been investigated. Translocation of the Tripeptides via hPEPT1 was determined in a MDCK/hPEPT1 cell-based translocation assay measuring substrate-induced changes in fluorescence of a membrane potential-sensitive probe. Affinities for hPEPT1 of relevant Tripeptides were determined by competition studies with [14C]Gly-Sar in MDCK/hPEPT1 cells. Forty Tripeptides were found to be substrates for hPEPT1, having K m app values in the range 0.4–28 mM. Eight Tripeptides were not able to cause a substrate-induced change in fluorescence in the translocation assay and seven Tripeptides interacted with the probe itself. The conformationally restricted tripeptide Met-Pro-Pro was identified as a novel high-affinity inhibitor of hPEPT1. We also discovered the first tripeptide (Asp-Ile-Arg) that was neither a substrate nor an inhibitor of hPEPT1. To rationalise the requirements for transport, a quantitative structure–activity relationship model correlating K m app values with VolSurf descriptors was constructed. This is, to our knowledge, the first predictive model for the translocation of Tripeptides via hPEPT1.
Riitta Korpela - One of the best experts on this subject based on the ideXlab platform.
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Effects of milk casein derived Tripeptides on endothelial enzymes in vitro; a study with synthetic Tripeptides.
Drug Research, 2012Co-Authors: Aino Siltari, Riitta Korpela, Anne S. Kivimäki, Pauliina I. Ehlers, Heikki VapaataloAbstract:In the fermentation of milk by certain lactic acid bacteria, casein is degraded into bioactive Tripeptides shown to lower blood pressure in experimental animal models and in mildly hypertensive humans. This effect is suggested to result mainly in inhibition of angiotensin converting enzyme 1 (ACE-1). Due to the complexity of renin-angiotensin system (RAS), several other enzymes than ACE-1 can participate in the production of vasoactive components. Therefore, in the present study we investigated effects of Tripeptides isoleucine-proline-proline (IPP), valine-proline-proline (VPP) and leucine-proline-proline (LPP) on some endothelial enzymes that are important in RAS or otherwise have a role in the endothelial function. The enzymes investigated were renin, chymase, neutral endopeptidase (NEP), prolyl oligopeptidase (POP), cathepsin G, endothelin converting enzyme 1 (ECE-1), and cyclooxygenase 1 and 2 (COX -1 and COX-2). The Tripeptides inhibited prolyl oligopeptidase (POP) dose-dependently. IPP was the most potent inhibitor (IC 50 486±95 µM). Contrary, cathepsin G was activated by IPP, VPP and LPP as well as the amino acids proline and isoleucine. The other investigated enzymes were not affected. Inhibition of POP and activation of cathepsin G do not explain the blood pressure lowering effects of the Tripeptides. Thus the inhibition of ACE-1 remains the most plausible mechanism of the antihypertensive effects of the Tripeptides.
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cardiovascular activity of milk casein derived Tripeptides and plant sterols in spontaneously hypertensive rats
Journal of Physiology and Pharmacology, 2009Co-Authors: Pauliina Jakala, E Pere, Risto Lehtinen, Anu M Turpeinen, Riitta Korpela, Heikki VapaataloAbstract:: The effect of chronic treatment with fermented milk products containing bioactive Tripeptides and plant sterols on blood pressure and vascular function was investigated in spontaneously hypertensive rats (SHR). Six-weeks old male SHR (n=36) were randomized into 4 groups by body weight and blood pressure to receive either Lactobacillus helveticus fermented standard milk product (containing Tripeptides Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro), test product with enzymatically produced Tripeptides without or with plant sterols or control product without the active constituents for 8 weeks. Systolic blood pressure (SBP) was measured weekly using the tail-cuff method. Thoracic aorta and mesenteric artery were excised for vascular response measurements. At the end, SBP values vs. control product group were: standard product group -14 mmHg (P<0.05), test product group -12 mmHg and test product +sterols group -7 mmHg. The average daily tripeptide dose was 2.8-5.2 mg/kg. Total serum cholesterol in the test product +sterols group tended to be lower than in the test product group (P=0.10) whereas serum plant sterol (campesterol, sitosterol) concentrations were higher (P<0.001). In conclusion, bioactive tripeptide-containing milk products attenuated the blood pressure development in SHR. The plant sterols did not improve this effect. Vascular responses did not markedly differ between the groups, except that endothelium-derived hyperpolarizing factor (EDHF) -related aortic relaxation was demonstrated in the test product +sterols group.
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casein derived bioactive Tripeptides ile pro pro and val pro pro attenuate the development of hypertension and improve endothelial function in salt loaded goto kakizaki rats
Journal of Functional Foods, 2009Co-Authors: Pauliina Jakala, Anu M Turpeinen, Riitta Korpela, Anne Hakala, Heikki VapaataloAbstract:Abstract Increased blood pressure and plasma cholesterol concentration are the major risk factors for cardiovascular diseases. We have previously shown that fermented milk products containing casein-derived bioactive Tripeptides, isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) partly inhibit the blood pressure increase in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of bioactive tripeptide-containing fermented milk products (with or without plant sterols) on blood pressure and vascular function in salt-loaded type 2 diabetic Goto–Kakizaki (GK) rats after 8 weeks’ treatment. The development of blood pressure was attenuated in the groups receiving tripeptide-containing products (−10 to −12 mmHg vs. the control product group, P
Jaehui Choi - One of the best experts on this subject based on the ideXlab platform.
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solid phase synthesis of kojic acid Tripeptides and their tyrosinase inhibitory activity storage stability and toxicity
Bioorganic & Medicinal Chemistry Letters, 2004Co-Authors: Jaehui ChoiAbstract:A small library of kojic acid-Tripeptides (Ko-X 1 X 2 X 3 ) was prepared by solid-phase parallel synthesis and assayed to evaluate their tyrosinase inhibitory activity. Most of the kojic acid-Tripeptides showed better activities than kojic acid. Kojic acid-FWY was the best compound, and it exhibited 100-fold tyrosinase inhibitory activity compared with kojic acid. In addition, their storage stabilities were approximately 15 times higher and their toxicity was lower than that of kojic acid.
Alan R Katritzky - One of the best experts on this subject based on the ideXlab platform.
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dbu catalyzed transprotection of n fmoc cysteine di and Tripeptides into s fm cysteine di and Tripeptides
Organic and Biomolecular Chemistry, 2011Co-Authors: Alan R Katritzky, Nader E Abodya, Abdelmotaal Abdelmajeid, Srinivasa R Tala, M S Amine, Said A ElfekyAbstract:The transprotection of N-Fmoc-cysteine containing di- and Tripeptides possessing a free SH group to produce the corresponding S-Fm-cysteine di- and Tripeptides bearing a free amino group is accomplished efficiently with DBU in dry THF. The N-Fmoc to S-Fm transformation mechanism is discussed. S-Fm-Cysteine di- and Tripeptides readily form amide bonds on coupling with N-(Pg-α-aminoacyl)benzotriazoles and N-(Pg-α-dipeptidoyl)benzotriazoles to give larger peptides.
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the efficient preparation of di and Tripeptides by coupling n cbz or fmoc α aminoacyl benzotriazoles with unprotected amino acids
Synthesis, 2006Co-Authors: Alan R Katritzky, Parul Angrish, Kazuyuki SuzukiAbstract:N-(Cbz- or Fmoc-a-aminoacyl)benzotriazoles 2 and N-protected peptidoylbenzotriazoles 6 are coupled in aqueous acetonitrile solution with free amino acids or dipeptides to prepare: (i) 22 chirally pure dipeptides 5a-v (in an average yield of 82%) from N-(Cbz- or Fmoc-a-aminoacyl)benzotriazoles 2 and unprotected amino acids, (ii) five chiral Tripeptides 7a-e (in an average yield of 75%) from N-protected peptidoylbenzotriazoles 6 and unprotected amino acids, (iii) one chiral tripeptide 7g (62%) from N-(Cbz- or Fmoc-a-aminoacyl)benzotriazole 2a and the free dipeptide 8. In all, N-(Cbz- or Fmoc-a-aminoacyl)benzotriazole derivatives of 17 of the 20 naturally occurring amino acids were used, including those containing the following unprotected side chain functionalities: alcoholic -OH (Ser), indole -NH (Trp), imidazole -NH, phenolic -OH (Tyr), -CONH 2 (Gin, Asn), -SH (Cys), -CO 2 H (Glu, Asp), and -S-S (Cystine). Support for the complete retention of chirality was obtained by parallel experiments involving D-Ala, L-Ala, and DL-Ala for the preparation of di- and Tripeptides. This and other evidence for chiral integrity was supported by NMR and HPLC analyses.
