Design, synthesis and biological evaluation of small molecule inhibitors of CD4-gp120 binding based on virtual screening

Judith M. Lalonde, Mark A. Elban, Joel R. Courter, Akihiro Sugawara, Takahiro Soeta, Navid Madani, Amy M. Princiotto, Young Do Kwon, Peter D. Kwong, Arne Schön, Ernesto Freire, Joseph Sodroski, Amos B. Smith

研究成果: Article査読

61 被引用数 (Scopus)

抄録

The low-molecular-weight compound JRC-II-191 inhibits infection of HIV-1 by blocking the binding of the HIV-1 envelope glycoprotein gp120 to the CD4 receptor and is therefore an important lead in the development of a potent viral entry inhibitor. Reported here is the use of two orthogonal screening methods, gold docking and ROCS shape-based similarity searching, to identify amine-building blocks that, when conjugated to the core scaffold, yield novel analogs that maintain similar affinity for gp120. Use of this computational approach to expand SAR produced analogs of equal inhibitory activity but with diverse capacity to enhance viral infection. The novel analogs provide additional lead scaffolds for the development of HIV-1 entry inhibitors that employ protein-ligand interactions in the vestibule of gp120 Phe 43 cavity.

本文言語English
ページ(範囲)91-101
ページ数11
ジャーナルBioorganic and Medicinal Chemistry
19
1
DOI
出版ステータスPublished - 2011 1 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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