Ligand binding analysis for human alpha5beta1 integrin: strategies for designing new alpha5beta1 integrin antagonists

Luciana Marinelli; Axel Meyer; Dominik Heckmann; Antonio Lavecchia; Ettore Novellino; Horst Kessler

doi:10.1021/jm040224i

Ligand binding analysis for human alpha5beta1 integrin: strategies for designing new alpha5beta1 integrin antagonists

J Med Chem. 2005 Jun 30;48(13):4204-7. doi: 10.1021/jm040224i.

Authors

Luciana Marinelli¹, Axel Meyer, Dominik Heckmann, Antonio Lavecchia, Ettore Novellino, Horst Kessler

Affiliation

¹ Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D. Montesano, 49-80131 Napoli, Italy.

PMID: 15974570
DOI: 10.1021/jm040224i

Abstract

We report a three-dimensional model of the alpha5beta1 integrin headgroup bound to the most potent and selective ligand (SJ749) known to date. The model was built using the comparative protein modeling method, and it is consistent with experimental data. From this study, we identified two potentially important regions in the alpha5beta1 receptor that are peculiar to this integrin and might be worth considering for drug targeting.

MeSH terms

Amino Acid Sequence
Binding Sites
Drug Design
Humans
Imidazoles / pharmacology
Integrin alpha5beta1 / antagonists & inhibitors*
Integrin alpha5beta1 / chemistry
Integrin alpha5beta1 / metabolism*
Ligands
Peptide Fragments / chemistry
Protein Conformation
Protein Subunits / chemistry
Protein Subunits / metabolism
Sequence Alignment

Substances

Imidazoles
Integrin alpha5beta1
Ligands
Peptide Fragments
Protein Subunits