10 抗腫瘍活性環状ヘキサペプチド,RA類のコンホメーション解析(口頭発表の部)

概要

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Conformational analysis of antitumor cyclic hexapeptide, RA series obtained from Rubia akane and R. cordifolia was studied by spectroscopic (NMR, CD, X-ray analysis) and computational chemical methods (molecular dynamics and molecular mechanics calculation). A conbination of different homo- and heteronuclear two-dimensional NMR techniques at 500MHz have enabled us to assign completely the ^1H and ^<13>C signals of the two conformers A and B of RA-VII in CDCl_3. The structures of three conformers (A, B and C) in DMSO-d_6 solution was also derived from 2D-NMR techniques, temperature dependences of NH protons and NOE experiments. Distances deduced from the NMR measurements were used for refinements by restrained molecular dynamics calculations using AMBER program. These conformational analysis found that these conformers were caused by geometrical isomerization and main populated conformer A exhibits a typical type II β-turn structure, which is similar to the crystal structure analyzed by X-ray. N-methyl derivative of RA-VII (RA-VII-NMe) exhibited the more weakly populated conformer A in solution may be responsible for its reduced biological activity in comparison to RA-VII. Further, the presence of highly strained 14-menbered ring was necessitated to maintain the typical type II β-turn structure appeared in conformer A and was considered to play an important part to show an antitumor activity.
天然有機化合物討論会の論文
1990-09-25