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The elongation factor eEF1A is a binding target for a novel, non‐hormonal male contraceptive
Author(s) -
Hutton Jenna Louise,
Gross Stephane,
Tash Joseph,
Kinzy Terri Goss
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.654.1
Subject(s) - hormone , nucleotide , infertility , biology , chemistry , biochemistry , genetics , pregnancy , gene
Hormone‐based oral contraceptives were approved for use in women in 1960 and have become a popular form of birth control. But oral contraceptives are not suitable for all women and other methods have a high failure rate when used incorrectly. According to WHO statistics, 42% of pregnancies are unintended, identifying a need for the development of alternative methods of contraception. Gamendazole (GMZ) was identified from a screen of indazole carboxylic acid analogues as a non‐hormonal compound that causes male infertility in rats. H2‐GMZ, a more potent analogue of GMZ, produced 100% infertility after a single 3mg/kg dose, with 100% reversibility within 6 weeks. Eukaryotic elongation factor 1A (eEF1A) was identified as a binding partner of GMZ. To gain insight into the mechanism of GMZ action, we examined the effect of the drug on the canonical and non‐canonical functions of eEF1A. Total translation rates and nucleotide binding were minimally affected, suggesting that GMZ functions via inhibition of eEF1A's actin bundling function. Co‐sedimentation assays using purified yeast actin and yeast or rabbit eEF1A showed inhibition of actin bundling in the presence of 10 uM GMZ. We are currently developing a light scattering assay to determine kinetics of bundling, reversibility of inhibition and effects of adding competing factors. Preliminary data shows 10 uM GMZ inhibits rabbit eEF1A's actin bundling function.