Conformationally constrained mimetics of laminin peptide YIGSR as precursors for antimetastatic disintegrins.
Conformationally constrained mimetics of the laminin cell-adhesion site, YIGSR, are described. The site is the natural antagonist of the integrin-associated laminin receptor 1 (LAMR1) known to mediate metastatic tumor adhesion. The attachment of selected metastatic cell lines toward the constrained antagonists has been assessed. Observed differential responses prompted by folding preferences of the mimetics revealed stronger attachment activities for turnlike structures. The results permit the conformational design of antimetastatic disintegrins.
Bella
Angelo
A
Department of Chemistry, University of Leicester, Leicester LE1 7RH, UK.
Lewis
Helen
H
Phu
Jennifer
J
Bottrill
Andrew R
AR
Mistry
Sharad C
SC
Pullar
Christine E
CE
Ryadnov
Maxim G
MG
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D019483:Disintegrins / Q000737:chemistry*; D005354:Fibrosarcoma / Q000188:drug therapy / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D007797:Laminin / Q000737:chemistry*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D017474:Receptors, Laminin / Q000037:antagonists & inhibitors; D012269:Ribosomal Proteins
D000970:Antineoplastic Agents; D019483:Disintegrins; D007797:Laminin; D009842:Oligopeptides; D010456:Peptides, Cyclic; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine