Conformational preferences of natural and C3-modified epothilones in aqueous solution

Máté Erdélyi; Bernhard Pfeiffer; Kurt Hauenstein; Jörg Fohrer; Jürg Gertsch; Karl-Heinz Altmann; Teresa Carlomagno

doi:10.1021/jm7013452

Conformational preferences of natural and C3-modified epothilones in aqueous solution

Máté Erdélyi
, Bernhard Pfeiffer
, Kurt Hauenstein
, Jörg Fohrer
, Jürg Gertsch
, Karl-Heinz Altmann
, Teresa Carlomagno

Biosciences

Research output: Contribution to journal › Article › peer-review

Abstract

The conformational properties of the microtubule-stabilizing agent epothilone A ( 1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a combination of NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The tubulin-bound conformation of epothilone A ( 1a), as previously proposed on the basis of solution NMR data, was found to represent a significant fraction of the ensemble of conformations present for the free ligands in aqueous solution.

Original language	English
Pages (from-to)	1469-73
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	5
DOIs	https://doi.org/10.1021/jm7013452
Publication status	Published - 13 Mar 2008

Keywords

Epothilones/chemistry
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Conformation
Monte Carlo Method
Solutions
Tubulin/chemistry
Water

Access to Document

10.1021/jm7013452

Cite this

@article{f837503cd9d3464f95b8feb446b27af2,

title = "Conformational preferences of natural and C3-modified epothilones in aqueous solution",

abstract = "The conformational properties of the microtubule-stabilizing agent epothilone A ( 1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a combination of NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The tubulin-bound conformation of epothilone A ( 1a), as previously proposed on the basis of solution NMR data, was found to represent a significant fraction of the ensemble of conformations present for the free ligands in aqueous solution.",

keywords = "Epothilones/chemistry, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Conformation, Monte Carlo Method, Solutions, Tubulin/chemistry, Water",

author = "M{\'a}t{\'e} Erd{\'e}lyi and Bernhard Pfeiffer and Kurt Hauenstein and J{\"o}rg Fohrer and J{\"u}rg Gertsch and Karl-Heinz Altmann and Teresa Carlomagno",

year = "2008",

month = mar,

day = "13",

doi = "10.1021/jm7013452",

language = "English",

volume = "51",

pages = "1469--73",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "5",

}

TY - JOUR

T1 - Conformational preferences of natural and C3-modified epothilones in aqueous solution

AU - Erdélyi, Máté

AU - Pfeiffer, Bernhard

AU - Hauenstein, Kurt

AU - Fohrer, Jörg

AU - Gertsch, Jürg

AU - Altmann, Karl-Heinz

AU - Carlomagno, Teresa

PY - 2008/3/13

Y1 - 2008/3/13

N2 - The conformational properties of the microtubule-stabilizing agent epothilone A ( 1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a combination of NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The tubulin-bound conformation of epothilone A ( 1a), as previously proposed on the basis of solution NMR data, was found to represent a significant fraction of the ensemble of conformations present for the free ligands in aqueous solution.

AB - The conformational properties of the microtubule-stabilizing agent epothilone A ( 1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a combination of NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The tubulin-bound conformation of epothilone A ( 1a), as previously proposed on the basis of solution NMR data, was found to represent a significant fraction of the ensemble of conformations present for the free ligands in aqueous solution.

KW - Epothilones/chemistry

KW - Magnetic Resonance Spectroscopy

KW - Models, Molecular

KW - Molecular Conformation

KW - Monte Carlo Method

KW - Solutions

KW - Tubulin/chemistry

KW - Water

U2 - 10.1021/jm7013452

DO - 10.1021/jm7013452

M3 - Article

C2 - 18271516

SN - 0022-2623

VL - 51

SP - 1469

EP - 1473

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 5

ER -

Conformational preferences of natural and C3-modified epothilones in aqueous solution

Abstract

Keywords

Access to Document

Fingerprint

Cite this