IDENTIFICATION OF THE ANTIADHESIVE SITE BURIED WITHIN THE HEPARIN-BINDING DOMAIN OF FIBRONECTIN

We recently found that heparin-binding domain 2 (Hep 2) of fibronectin (FN) exhibits cryptic anti-adhesive activity. In order to locate the anti-adhesive site, a number of synthetic peptides which represent the primary structure of the Hep 2 domain were characterized as to their ability to decrease the adhesion of A375SM melanoma cells to FN substr ate. Only one peptide (T-E-A-T-I-T-G-L-E-P-G-T-E-Y-T-I-Y-V-I-A-L resid ues 1835-1855) (peptide III14-2), which is situated between the previo usly identified adhesive sites, FN-C/H-I and II, decreased the cell ad hesion to FN. Assaying of the anti-adhesive activities of sub-peptides showed that the hydrophobic moiety of peptide III14-2 (underlined seq uence) seems to be indispensable for the anti-adhesive activity. These results suggest that anti-adhesive activity is closely associated wit h the sequence, Y-T-I-Y-V-I-A-L, that is usually buried within the Hep 2 domain structure because of its hydrophobic nature.