Determination of peptide hydrophobicity parameters by reversed-phase high-performance liquid chromatography

The log kw values of fourteen potential fibrinogen receptor antagonist peptides (RGDX) determined by reversed-phase HPLC were correlated to hydrophobic parameters of the amino acid side-chain log P in position X of the tetrapeptides. Comparing the polymer columns with LiChrosorb RP-8, the correlation coefficient using a polyethylene column is higher (0.94) than that for RP-8 (0.88), which demonstrates the importance of a homogeneous hydrophobic surface and makes this method very suitable for the determination of the overall hydrophobicity of shorter peptides. The hydrophobicity parameters log kw of the RGDX peptides (-1.15 to 2.19) were used to investigate the influence of molecular parameters of X on the potency of RGDX in inhibiting platelet aggregation. The results confirm the importance of hydrophobicity for the contribution of X to the biological activity of RGDX.