M. Zhao et al., SYNTHETIC LAMININ-LIKE PEPTIDES AND PSEUDOPEPTIDES AS POTENTIAL ANTIMETASTATIC AGENTS, Journal of medicinal chemistry, 37(20), 1994, pp. 3383-3388
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.