Issue 13, 2008

A comparative study on the experimentally derived electron densities of three protease inhibitor model compounds

Abstract

In order to contribute to a rational design of optimised protease inhibitors which can covalently block the nucleophilic amino acids of the proteases' active sites, we have chosen three model compounds (aziridine l, oxirane 2 and acceptor-substituted olefin 3) for the examination of their electron-density distribution. Therefore, high-resolution low temperature (9, 27 and 100 K) X-ray diffraction experiments on single-crystals were carried out with synchrotron and conventional X-radiation. It could be shown by the analysis of the electron density using mainly Bader's Theory of Atoms in Molecules, Volkov's EPMM method for interaction energies, electrostatic potentials and Gatti's Source Function that aziridine l is most suitable for drug design in this field. A regioselective nucleophilic attack at carbon atom C1 could be predicted and even hints about the reaction's stereoselectivity could be obtained. Moreover, the comparison between two data sets of aziridine l (conventional X-ray source vs. synchrotron radiation) gave an estimate concerning the reproducibility of the quantitative results.

Graphical abstract: A comparative study on the experimentally derived electron densities of three protease inhibitor model compounds

Supplementary files

Article information

Article type
Paper
Submitted
19 Feb 2008
Accepted
28 Mar 2008
First published
02 May 2008

Org. Biomol. Chem., 2008,6, 2295-2307

A comparative study on the experimentally derived electron densities of three protease inhibitor model compounds

S. Grabowsky, T. Pfeuffer, W. Morgenroth, C. Paulmann, T. Schirmeister and P. Luger, Org. Biomol. Chem., 2008, 6, 2295 DOI: 10.1039/B802831A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements