New analogues of laminin active fragment YIGSR: synthesis and biological activity in vitro and in vivo.
Eleven analogues of the laminin pentapeptide amide fragment Tyr-Ile-Gly-Ser-Arg-NH2 (YIGSR-NH2) corresponding to a B1 chain fragment of the glycoprotein laminin have been synthesized by the solid phase method, and their biological activity has been studied in vitro by a cell adhesion assay: all of them inhibited the adhesion of LLC tumor cells to laminin. The analogues were found to be more resistant to enzymatic degradation in human serum than YIGSR-NH2 itself. Analogue DatIGSHar-NH2 was selected for an experimental pulmonary metastasis assay in vivo: it had higher antimetastatic activity than YIGSR-NH2.
Witkowska
Ewa
E
Laboratory of Peptides, Department of Chemistry, Warsaw University, Poland. ewawit@chem.uw.edu.pl
Oriowska
Alicja
A
Izdebski
Jan
J
Salwa
Jan
J
Wietrzyk
Joanna
J
Opolski
Adam
A
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D007797:Laminin / Q000737:chemistry*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007797:Laminin; D009842:Oligopeptides; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine