Migration of monocytes in the presence of elastolytic fragments of elastin and in synthetic derivates. Structure-activity relationships.

YGVG and GLVPG, two new chemokinetic peptides, were identified in elastolytic digests of elastin, besides the known chemoattractant hexapeptide VGVAPG. In order to identify possible sequences responsible for the chemotactic and chemokinetic activities and to obtain structure-activity relationships we synthesized some analogues of these peptides: FGVG (an analogue of YGVG), GVAPG and VGAPG (derived from the hexapeptide by deletion of Val1 or Val3). FGVG has a higher chemotactic activity than YGVG (chemotactic indices of 0.62 and 0.49, respectively, at 10(-11) M) and is both chemotactic and chemokinetic. Checkerboard analysis demonstrated that both peptides derived from the hexapeptide present, in addition to the chemotactic activity, a chemokinetic activity. The chemotactic index of GVAPG is 0.66 at 10(-10) M, while for VGAPG it is 0.86 at 10(-9) M. These results indicate that the deletion of the N-terminal residue of the elastin chemotactic peptides, VGVAPG and GFGVG, gives rise to chemokinetic activity. CD and NMR studies showed that all peptides are largely unordered in aqueous solution.