SYNTHETIC LAMININ-LIKE PEPTIDES AND PSEUDOPEPTIDES AS POTENTIAL ANTIMETASTATIC AGENTS

This paper describes our efforts to study structure-activity relations hips, improve the antimetastatic potency, and limit the in vivo enzyma tic degradation of YIGSR-NH2, a synthetic peptide from the B1 chain of laminin, which reportedly has potential as an antimetastatic agent. T o this end we have synthesized a series of psi(CH2NH) peptide analogs (5-9) of YIGSR-NH2 and a number of peptides in which the Tyr residue w as replaced with D-Tyr (1), Phe (2), Phe (p-F) (3), and Phe(p-NH2) (4) . All new peptides were assayed in vitro for their ability to promote cell attachment in both B16F10 mouse melanoma cells and HT-1080 human fibrosarcoma cells. On the basis of the in vitro assay results, peptid es 3-5, 8, and 9 were tested in vivo for their ability to inhibit tumo r metastasis to the lungs in mice that were coinjected in the tail vei n with B16F10 melanoma cells and 1 mg of peptide. In summary, of the n ine new peptides only the Phe(p-NH2) peptide 4 showed consistent in vi tro cell attachment activity, but only low in vivo antimetastatic acti vity.