SMM-chemokines: A class of unnatural synthetic molecules as chemical probes of chemokine receptor biology and leads for therapeutic development

Santosh Kumar, Won Tak Choi, Chang Zhi Dong, Navid Madani, Shaomin Tian, Dongxiang Liu, Youli Wang, James Pesavento, Jun Wang, Xuejun Fan, Jian Yuan, Wayne R. Fritzsche, Jing An, Joseph G. Sodroski, Douglas D. Richman, Ziwei Huang

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Chemokines and their receptors play important roles in numerous physiological and pathological processes. To develop natural chemokines into receptor probes and inhibitors of pathological processes, the lack of chemokine-receptor selectivity must be overcome. Here, we apply chemical synthesis and the concept of modular modifications to generate unnatural synthetically and modularly modified (SMM)-chemokines that have high receptor selectivity and affinity, and reduced toxicity. A proof of the concept was shown by transforming the nonselective viral macrophage inflammatory protein-II into new analogs with enhanced selectivity and potency for CXCR4 or CCR5, two principal coreceptors for human immunodeficiency virus (HIV)-1 entry. These new analogs provided insights into receptor binding and signaling mechanisms and acted as potent HIV-1 inhibitors. These results support the concept of SMM-chemokines for studying and controlling the function of other chemokine receptors.

Original languageEnglish (US)
Pages (from-to)69-79
Number of pages11
JournalChemistry and Biology
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Kumar, S., Choi, W. T., Dong, C. Z., Madani, N., Tian, S., Liu, D., Wang, Y., Pesavento, J., Wang, J., Fan, X., Yuan, J., Fritzsche, W. R., An, J., Sodroski, J. G., Richman, D. D., & Huang, Z. (2006). SMM-chemokines: A class of unnatural synthetic molecules as chemical probes of chemokine receptor biology and leads for therapeutic development. Chemistry and Biology, 13(1), 69-79. https://doi.org/10.1016/j.chembiol.2005.10.012