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 elas tolytic digests of elastin, besides the known chemoattractant hexapept ide VGVAPG. In order to identify possible sequences responsible for th e chemotactic and chemokinetic activities and to obtain structure-acti vity relationships we synthesized some analogues of these peptides: FG VG (an analogue of YGVG), GVAPG and VGAPG (derived from the hexapeptid e by deletion of Val(1) or Val(3)). FGVG has a higher chemotactic acti vity than YGVG (chemotactic indices of 0.62 and 0.49, respectively, at 10(-11) M) and is both chemotactic and chemokinetic. Checkerboard ana lysis demonstrated that both peptides derived from the hexapeptide pre sent, 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 t he 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. (C) Munks gaard 1994.