Exploring the requirements for the hydrophobic scaffold and polar amine in inhibitors of M2 from influenza A virus

Jun Wang, Chunlong Ma, Victoria Balannik, Lawrence H. Pinto, Robert A. Lamb, William F. Degrado

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Inhibitors targeting the influenza A virus M2 (A/M2) proton channel have lost their effectiveness due to widespread resistance. As a first step in the development of new inhibitors that address this problem, we have screened several focused collections of small molecules using two-electrode voltage patch clamp assays (TEVC) on Xenopus laevis oocytes. Diverse head groups and scaffolds of A/M2 inhibitors have been explored. It has been found that not only amine but also hydroxyl, aminooxyl, guanidine, and amidine compounds are active against the A/M2 proton channel. Moreover, the channel is able to accommodate a wide range of structural variation in the apolar scaffold. This study offers information to guide the next generation of A/M2 proton channel inhibitor design.

Original languageEnglish (US)
Pages (from-to)307-312
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume2
Issue number4
DOIs
StatePublished - Apr 14 2011
Externally publishedYes

Keywords

  • A/M2 channel inhibitor
  • Influenza A/M2
  • two-electrode voltage clamp assay (TEVC)

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Exploring the requirements for the hydrophobic scaffold and polar amine in inhibitors of M2 from influenza A virus'. Together they form a unique fingerprint.

  • Cite this