Isolation and structure of antagonists of chemokine receptor (CCR5).

Published

Journal Article

Human CCR5 is a G-coupled receptor that binds to the envelope protein gp120 and CD4 and mediates the HIV-1 viral entry into the cells. The blockade of this binding by a small molecule receptor antagonist could lead to a new mode of action agent for HIV-1 and AIDS. Screening of natural product extracts led to the identification of anibamine (1), a novel pyridine quaternary alkaloid as a TFA salt, from Aniba sp.; ophiobolin C from fermentation extracts of fungi Mollisia sp.; and 19,20-epoxycytochalasin Q from Xylaria sp. Formation of the TFA salt of anibamine is plausibly an artifact of the isolation. The identity of the natural counterion is unknown. Anibamine.TFA competed for the binding of 125I-gp120 to human CCR5 with an IC50 of 1 microM. Ophiobolin C and 19,20-epoxycytochalasin Q exhibited binding IC50) values of 40 and 60 microM, respectively.

Full Text

Duke Authors

Cited Authors

  • Jayasuriya, H; Herath, KB; Ondeyka, JG; Polishook, JD; Bills, GF; Dombrowski, AW; Springer, MS; Siciliano, S; Malkowitz, L; Sanchez, M; Guan, Z; Tiwari, S; Stevenson, DW; Borris, RP; Singh, SB

Published Date

  • June 2004

Published In

Volume / Issue

  • 67 / 6

Start / End Page

  • 1036 - 1038

PubMed ID

  • 15217290

Pubmed Central ID

  • 15217290

International Standard Serial Number (ISSN)

  • 0163-3864

Digital Object Identifier (DOI)

  • 10.1021/np049974l

Language

  • eng

Conference Location

  • United States