Structural analysis of a novel small molecule ligand bound to the CXCL12 chemokine

Emmanuel W. Smith, Yan Liu, Anthony E. Getschman, Francis C. Peterson, Joshua J. Ziarek, Rongshi Li, Brian F. Volkman, Yu Chen

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

CXCL12 binds to CXCR4, promoting both chemotaxis of lymphocytes and metastasis of cancer cells. We previously identified small molecule ligands that bind CXCL12 and block CXCR4-mediated chemotaxis. We now report a 1.9 Å resolution X-ray structure of CXCL12 bound by such a molecule at a site normally bound by sY21 of CXCR4. The complex structure reveals binding hot spots for future inhibitor design and suggests a new approach to targeting CXCL12-CXCR4 signaling in drug discovery.

Original languageEnglish (US)
Pages (from-to)9693-9699
Number of pages7
JournalJournal of Medicinal Chemistry
Volume57
Issue number22
DOIs
StatePublished - Nov 26 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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