title: Arg-Gly-Asp constrained within cyclic pentapeptides. Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1.
abstract: Cyclic Arg-Gly-Asp-Phe-Val peptides with either D-Phe or D-Val residues were 20- to more than 100-fold better inhibitors of cell adhesion to vitronectin and/or laminin fragment P1 when compared to a linear variant or Gly-Arg-Gly-Asp-Ser. No or only little increase in inhibitory capacity was observed for fibronectin adhesion and for the binding of platelet receptor alpha IIb beta 3 to fibrinogen. NMR studies of the two most active cyclic peptides showed for both an all-trans conformation with a beta II' and gamma turn. Subtle conformational differences, however, exist between both peptides and may contribute to selectivity of inhibition.
authors.affiliation: Max-Planck-Institut für Biochemie, Martinsried, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Aumailley
authors.forename: M
authors.initials: M
authors.lastname: Gurrath
authors.forename: G
authors.initials: G
authors.lastname: Müller
authors.forename: J
authors.initials: J
authors.lastname: Calvete
authors.forename: R
authors.initials: R
authors.lastname: Timpl
authors.forename: H
authors.initials: H
authors.lastname: Kessler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D019096:Vitronectin
chemical_list: D006023:Glycoproteins; D016023:Integrins; D007797:Laminin; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019096:Vitronectin; C047981:arginyl-glycyl-aspartic acid