Conformational analysis of dolastatin 10: An nmr and theoretical approach

✍ Scribed by E. Benedetti; T. Carlomagno; F. Fraternali; Y. Hamada; K. Hayashi; L. Paolillo; T. Shioiri

• Publisher: Wiley (John Wiley & Sons)
• Year: 1995
• Tongue: English
• Weight: 865 KB
• Volume: 36
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.360360414

✦ Synopsis

Abstract

A solution conformational analysis of dolastatin 10, a powerful antineoplaslic agent, has been carried out by means of nmr techniques and theoretical calculations. ^1^H mono‐ and bidimensional nmr experiments, as well as ^1^H‐^13^C heterocorrelated spectra, have been performed on CD~2~Cl~12~ solutions. The most interesting nmr data is a huge shielding of the aCH (25) proton of the Dov residue, suggesting the presence of an interaction between the N‐terminal and the aromatic C‐terminal ends of the molecule.

The possibility of a head‐to‐tail intermolecular association having been discarded, the presence of a series of preferred folded conformation has been hypothesized. Conformational theoretical analysis supports the nmr hypothesis of a folded peptide‐like molecule, and a series of possible conformers in good agreement with the experimental data have been analyzed. © 1995 John Wiley & Sons, Inc.