Interpreting the behavior of concentration-response curves of hyaluronidase inhibitors under DMSO-perturbed assay conditions

Keisuke Tomohara, Tomohiro Ito, Saika Onikata, Kota Furusawa, Atsushi Kato, Isao Adachi

研究成果: ジャーナルへの寄稿学術誌査読

7 被引用数 (Scopus)

抄録

Hyaluronan-degrading enzyme (hyaluronidase) is involved in tumor growth and inflammation, and as such, hyaluronidase inhibitors have received recent attention as potential therapeutics. The previous studies have successfully discovered a wide range of inhibitors, but unfortunately most of them are dissimilar to original ligand hyaluronan and the mode of action is poorly understood. The present study mechanistically characterized these structurally unrelated inhibitors by interpreting the behavior of concentration-response curves under several in vitro assay conditions. Detergent-addition conditions definitely identified aggregation-based inhibitors. Subsequently, DMSO-perturbed conditions, though preliminary, highlighted the inhibitors that might bind to enzyme non-specifically. Here, an intriguing implication of the latter description is that DMSO-perturbed conditions would generate non-productive but not-denatured enzyme that is an assembly of effective species to capture non-specific binding molecules, and thereby would attenuate their inhibitory activities.

本文言語英語
ページ(範囲)3153-3157
ページ数5
ジャーナルBioorganic and Medicinal Chemistry Letters
26
13
DOI
出版ステータス出版済み - 7月 1 2016
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 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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