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

41 Citations (Scopus)

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

Fingerprint

Influenza A virus
Viruses
Scaffolds
Amines
Protons
Amidines
Guanidine
Xenopus laevis
Hydroxyl Radical
Oocytes
Clamping devices
Electrodes
Head
Assays
Molecules
Electric potential

Keywords

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

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Exploring the requirements for the hydrophobic scaffold and polar amine in inhibitors of M2 from influenza A virus. / Wang, Jun; Ma, Chunlong; Balannik, Victoria; Pinto, Lawrence H.; Lamb, Robert A.; Degrado, William F.

In: ACS Medicinal Chemistry Letters, Vol. 2, No. 4, 14.04.2011, p. 307-312.

Research output: Contribution to journalArticle

Wang, Jun ; Ma, Chunlong ; Balannik, Victoria ; Pinto, Lawrence H. ; Lamb, Robert A. ; Degrado, William F. / Exploring the requirements for the hydrophobic scaffold and polar amine in inhibitors of M2 from influenza A virus. In: ACS Medicinal Chemistry Letters. 2011 ; Vol. 2, No. 4. pp. 307-312.
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