1. Academic Validation
  2. Dual structure-activity relationship of osteoclastogenesis inhibitor methyl gerfelin based on TEG scanning

Dual structure-activity relationship of osteoclastogenesis inhibitor methyl gerfelin based on TEG scanning

  • Bioconjug Chem. 2013 Jan 16;24(1):44-52. doi: 10.1021/bc3003666.
Naoki Kanoh 1 Takahiro Suzuki Makoto Kawatani Yasuhiro Katou Hiroyuki Osada Yoshiharu Iwabuchi
Affiliations

Affiliation

  • 1 Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. [email protected]
Abstract

Methyl gerfelin derivatives, each having an amine-terminated tri(ethylene glycol) linker at the peripheral position, were designed and systematically synthesized. These "TEGylated" derivatives were then subjected to a structure-activity relationship (SAR) study to examine their glyoxalase 1-inhibition activity and binding affinity toward the three binding proteins identified. Among the derivatives synthesized, that with a NH(2)-TEG linker at the C6-methyl group showed the most potent glyoxalase 1-inhibiting activity and glyoxalase 1 selectivity. These results indicated that derivatization at the C6-methyl group would be suitable for the further development of selective glyoxalase 1 inhibitors.

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