Skip Navigation


PEDS Advance Access originally published online on January 4, 2008
Protein Engineering Design and Selection 2008 21(2):65-72; doi:10.1093/protein/gzm079
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
21/2/65    most recent
gzm079v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Gaertner, H.
Right arrow Articles by Hartley, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gaertner, H.
Right arrow Articles by Hartley, O.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Highly potent HIV inhibition: engineering a key anti-HIV structure from PSC-RANTES into MIP-1β/CCL4

Hubert Gaertner1, Olivier Lebeau1, Irène Borlat1, Fabrice Cerini1, Brigitte Dufour1, Gabriel Kuenzi1, Astrid Melotti1, Richard J. Fish1,4, Robin Offord1,3, Jean-Yves Springael2, Marc Parmentier2 and Oliver Hartley1,5

1Department of Structural Biology and Bioinformatics, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Geneva 4, Switzerland 2 Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), ULB Campus Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium 3Mintaka Foundation for Medical Research, 14 chemin des Aulx, 1228 Plan-les Ouates, Switzerland

5 To whom correspondence should be addressed. E-mail: oliver.hartley{at}medecine.unige.ch

The HIV coreceptor CCR5 is a validated target for both the prevention and therapy of HIV infection. PSC-RANTES, an N-terminally modified analogue of one of the natural chemokine ligands of CCR5 (RANTES/CCL5), is a potent inhibitor of HIV entry into target cells. Here, we set out to engineer the anti-HIV activity of PSC-RANTES into another natural CCR5 ligand (MIP-1β/CCL4), by grafting into it the key N-terminal pharmacophore region from PSC-RANTES. We were able to identify MIP-1β/CCL4 analogues that retain the receptor binding profile of MIP-1β/CCL4, but acquire the very high anti-HIV potency and characteristic inhibitory mechanism of PSC-RANTES. Unexpectedly, we discovered that in addition to N-terminal structures from PSC-RANTES, the side chain of Lys33 is also necessary for full anti-HIV potency.

Keywords: CCR5/HIV coreceptor/MIP-1β CCL4/pharmacophore grafting/PSC-RANTES

Received July 12, 2007; revised October 3, 2007; accepted November 4, 2007.

4 Present address: Service of Angiology and Hemostasis, Department of Internal Medicine, Geneva University Hospital, 24, rue Micheli-du Crest, 1211 Geneva 4, Switzerland


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.