title: Solution structure of a biologically active cyclic LDV peptide analogue containing a type II' beta-turn mimetic.
abstract: The solution structure of cyclo-[Gly-Leu-Asp-Val-BTD] (BTD = beta-turn dipeptide) has been determined by two-dimensional 1H-NMR (nuclear magnetic resonance) spectroscopy and systematic conformational searching combined with molecular dynamics studies. The structure contains two hydrogen bonds between the Gly and Val residues, and a type I beta-turn with Leu and Asp at the (i + 1) and (i + 2) positions of the turn. The cyclic compound shows activity in a scintillation proximity assay (SPA) for the inhibition of the interaction between the integrin alpha 4 beta 1 and vascular cell adhesion molecule-1 (VCAM-I). The structure-activity relationship of the LDV sequence is discussed.
authors.affiliation: Wellcome Research Laboratories, Wellcome Foundation Ltd, Beckenham, Kent, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Doyle
authors.forename: J C
authors.initials: JC
authors.lastname: Harris
authors.forename: C M
authors.initials: CM
authors.lastname: Moody
authors.forename: P J
authors.initials: PJ
authors.lastname: Sadler
authors.forename: M
authors.initials: M
authors.lastname: Sims
authors.forename: J M
authors.initials: JM
authors.lastname: Thornton
authors.forename: J
authors.initials: J
authors.lastname: Uppenbrink
authors.forename: J H
authors.initials: JH
authors.lastname: Viles
mesh_terms: D003001:Cloning, Molecular; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry; D006860:Hydrogen Bonding; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D019010:Vascular Cell Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D004151:Dipeptides; D039041:Integrin alpha4beta1; D016023:Integrins; D010456:Peptides, Cyclic; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1