Abstracts of Poster Section C

• Publisher: Wiley (John Wiley & Sons)
• Year: 2005
• Tongue: English
• Weight: 450 KB
• Volume: 80
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20325

✦ Synopsis

As a part of a research proposal aimed at studying structure activity relationship (SAR) of peptides inhibitors for thrombin, we performed molecular docking experiments using the software "SCULPT" (from MDL) and designed "in silico" libraries of peptides as potential inhibitors for thrombin. Two classes of sequences were used to generate new peptides candidate inhibitors: 1-DPhe (P3)-Pro (P2)-Arg (P1)-D-Pro (P1')-P2'-CONH 2 and 2-DPhe-Pro-dArg-P1'-CONH 2 . Both the use of D-Pro in the P1' Position and the use of D-Arg instead of Arg in the P1 Position was shown to inhibit the hydrolysis of peptides, allowing these sequences to function as inhibitors [1]. Circular dichroism investigations showed that the D-Arg-in iϩ3 position followed by D-amino acids (polar and neutral like D-Thr, D-Gln, D-Ser and D-Ala) or L-Pro in iϩ4 position favors beta turn II and II' conformation in solution at low and neutral pH. SAR supports the hypothesis that tetrapeptides folded as beta turn conformation in solution are more active toward inhibiting thrombin. The significant differences between the Kis of tetrapeptides from the series D-Phe-Pro-D-Arg-P1'-CONH 2 suggests that the interaction between the amino acid at P1' position and the S1' pocket in thrombin is very specific and requires small, hydrophobic and polar amino-acids in P1'[1].