The cell adhesion domain, arginine-glycine-aspartic acid (RGD), has been incorporated into synthetic peptides to perform either of two modes of drug action, antagonist or agonist. Short, conformationally constrainedpeptides have been developed as antagonists for the platelet membrane glycoprotein complex, the integrin ( Y ~~~~~. using cell-based and integrin-based assays. In combination with a comparative molecular modeling study, these results have helped identrfy common conformational elements in thepharmacophore of this class of molecules. Peptides are presented that are highly potent, integrin specijic, and that possess reduced pharmacological side effects. Also presented is the development of a peptide that modijies, noncovalently, the surfaces ofa wide variety of synthetic materials used in medical implants. The agonist activity of this molecule is evident from its ability to stimulate cell attachment on these surfaces. This is shown to translate into an in vivo activity offaster and more complete tissue integration, and a reduction in foreign body response. 0 1995 John Wiley & Sons, Inc. ~~~~ Also, the figure legend for Figure 14 was reversed. It is here printed appropriately with the figure.
FIGURE 14 Cell infiltration and inflammatory response of a 21-day subcutaneous dacron mesh implant. (A) Peptite-2000 coated dacron implant. (B) Uncoated dacron implant. The arrows indicate giant cells due to an inflammatory response.