Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres
Tetsuo Narumi1, Ryoko Hayashi, Kenji Tomita
1Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Abstract:
A set of cyclic peptide analogues of a selective CXCR4 antagonist FC131 [cyclo(-d-Tyr-Arg-Arg-Nal-Gly-)] were synthesized and bioevaluated. Using (E)-alkene and (Z)-fluoroalkene dipeptide isosteres for Arg-Arg and Arg-Nal substructures, indispensable or the partial contribution of the two peptide bonds to the CXCR4 antagonism and anti-HIV activity was demonstrated. FC131 and the analogues were shown to selectively inhibit SDF-1 binding to CXCR4, whereas no inhibition of binding of SDF-1 to CXCR7 was observed.
More Related Videos
07:41A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
11:44Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
Published on: October 2, 2018
Related Concept Videos
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
01:29Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry