Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
See all formats and pricing
More options …
Volume 383, Issue 7-8

Issues

(R)-3-Amidinophenylalanine-Derived Inhibitors of Factor Xa with a Novel Active-Site Binding Mode

M. M. Mueller / S. Sperl / J. Stürzebecher / W. Bode / L. Moroder
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2002.130

Abstract

A putative nonsubstrate like binding mode of (R)-3- amidinophenylalanine derivatives to factor Xa, as derived from modeling experiments based on Xray analysis of their complexes with trypsin, was used to design a new generation of inhibitors. However, the resulting inhibitory potencies were not at all consistent with the working assumption, although with an adamantylureido derivative of (R)-3-amidinophenylalanine phenetyl amide a highly selective nanomolar inhibition of factor Xa was achieved. The Xray analysis of the complex of this ligand with factor Xa revealed an unexpected new binding mode, of which the most important feature is the interaction of the Cterminal aryl moiety with a hydrophobic subregion of the S1 subsite, while the adamantyl group occupies the hydrophobic S3/S4 subsites of the enzyme.

About the article

Published Online: 2005-06-01

Published in Print: 2002-08-27


Citation Information: Biological Chemistry, Volume 383, Issue 7-8, Pages 1185–1191, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2002.130.

Export Citation

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Nirav R. Patel, Dushyant V. Patel, Prashant R. Murumkar, and Mange Ram Yadav
European Journal of Medicinal Chemistry, 2016, Volume 121, Page 671
[2]
E. Prabhu Raman, Wenbo Yu, Sirish K. Lakkaraju, and Alexander D. MacKerell
Journal of Chemical Information and Modeling, 2013, Volume 53, Number 12, Page 3384
[3]
Daniel Rauh, Gerhard Klebe, and Milton T. Stubbs
Journal of Molecular Biology, 2004, Volume 335, Number 5, Page 1325
[4]
Daniel Rauh, Gerhard Klebe, Jörg Stürzebecher, and Milton T. Stubbs
Journal of Molecular Biology, 2003, Volume 330, Number 4, Page 761
[5]
Sochanchingwung Rumthao, Oukseub Lee, Qi Sheng, WenTao Fu, Debbie C. Mulhearn, David Crich, Andrew D. Mesecar, and Michael E. Johnson
Bioorganic & Medicinal Chemistry Letters, 2004, Volume 14, Number 20, Page 5165
[6]
Narender Singh and James M. Briggs
Biopolymers, 2008, Volume 89, Number 12, Page 1104
[7]
K. Schrör
Der Internist, 2005, Volume 46, Number 8, Page 873

Comments (0)

Please log in or register to comment.
Log in