Design and Synthesis of N-terminal Cyclic Motilin Partial Peptides : A Novel Pure Motilin Antagonist

概要

論文の詳細を見る
Motilin antagonist was designed and synthesized on the basis of the structure-activity relationship analysis of porcine motilin that we reported recently. The drug design was performed on a specific concept to reduce a flexibility of peptide conformation of porcine motilin partial peptide by its cyclization. The cyclic peptide was synthesized using Boc(tert-butyloxycarbonyl)solid phase methodology, followed by cyclization using the azide procedure, and tested for the binding activity to motilin receptor and smooth muscle contractile activity. The cylic peptides 3, 4, and 5 showed antagonistic property on contraction assay(pA_2[the negative logarithm of molar concentration of antagonist causing a 2-hold shift to the right of the concentration-response curve for motilin]: 4.5, 4.34, and 4.04, respectively, in rabbit duodenum)and no contractile activity even at high concentration.
公益社団法人日本薬学会の論文
2001-01-01