Thrombin is now known to mediate a number of potent biological effects on
cells bearing high-affinity thrombin receptors. These effects depend, at
least in part, upon receptor occupancy signals generated by thrombin's
interaction with the high affinity thrombin receptor. The present
inventors have formulated synthetic thrombin derivatives capable of
selectively stimulating or inhibiting thrombin receptor occupancy signals.
The stimulatory thrombin derivatives to bind to cell surface thrombin
receptors and stimulate DNA synthesis in cells treated with non-mitogenic
concentrations of alpha-thrombin or phorbol myristate acetate. Thus, these
peptides, which have both a thrombin receptor binding domain and a segment
of amino acids with a sequence common to a number of serine proteases,
appear to generate receptor-occupancy dependent mitogenic signals. The
inhibitory derivatives, which have no serine esterase conserved amino acid
sequences bind to thrombin receptors without generating receptor-occupancy
dependent mitogenic signals. This invention describes the peptides and
methods for using them to promote cell growth and wound healing or to
inhibit scar formation, tissue adhesions, and tumor metastasis and
angiogenesis.