1993 Fiscal Year Final Research Report Summary
Analysis of Structure-Activity Relationship of Peptides as Inhibitors of Platelet Aggregation
| Project/Area Number |
04660141
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
製造化学・食品
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
AKAMATSU Miki Kyoto University, Agriculture, Instructor, 農学部, 助手 (70183134)
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| Project Period (FY) |
1992 – 1993
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| Keywords | RGD / Arg-Gly-Asp / Inhibition of Platelet Aggregation / Hydrophobicity of Peptides / Partition Coefficient / 1-Octanol / Water |
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| Research Abstract |
1. The compounds were synthesized by the solid-phase method using Fmoc-amino acids. Effects of the test compounds were measured in human platelet rich plasma (PRP) as the inhibition of ADP-mediated platelet aggregation. We examined the inhibitory activity values of a series of RGDX.Previously, we proposed the pi_<alpha> value as a hydrophobicity index for amino acid side chain based on the analysis of the partition coefficients of N-acetyl peptide amides in the 1-octanol/water system. It was indicated that the inhibitory activity of peptides increased with the pi_<alpha> value of the residue X.However, in general the activity of peptides in which the side chain of the residue X is an alkyl group was lower than that of peptides including the residue X with an aromatic ring, suggesting the steric effect of the X side chain for the activity.
2. The inhibitory activity of some peptides is enhanced by elimination of the amino group of the Arg residue and by substitution of the amide bond of Arg-Gly with methylene. We synthesized this type of peptide mimetics with other nitrogen-containing groups instead of guanidino group of Arg and measured the inhibitory activity. We calculated the interaction energy of the nitrogen-containing cations in ligands with a carboxylate anion in the receptor by ab initio calculation to examine the correlation between the energy and the activity. The greater the interaction energy, the higher the inhibitory activity seemed to be.
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