2. Academic Validation
  3. 4-Substituted boro-proline dipeptides: synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities

4-Substituted boro-proline dipeptides: synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities

  • Bioorg Med Chem Lett. 2012 Sep 1;22(17):5536-40. doi: 10.1016/j.bmcl.2012.07.033.
Wengen Wu 1,  Yuxin Liu,  Lawrence J Milo Jr,  Ying Shu,  Peng Zhao,  Youhua Li,  Iwona Woznica,  Gengli Yu,  David G Sanford,  Yuhong Zhou,  Sarah E Poplawski,  Beth A Connolly,  James L Sudmeier,  William W Bachovchin,  Jack H Lai
Affiliations

Affiliation

  • 1 Tufts University School of Medicine, Department of Biochemistry, 136 Harrison Ave., Boston, MA 02111, United States.
PMID: 22853995 DOI: 10.1016/j.bmcl.2012.07.033
Abstract

The boroProline-based dipeptidyl boronic acids were among the first DPP-IV inhibitors identified, and remain the most potent known. We introduced various substitutions at the 4-position of the boroProline ring regioselectively and stereoselectively, and incorporated these aminoboronic acids into a series of 4-substituted boroPro-based dipeptides. Among these dipeptidyl boronic acids, Arg-(4S)-boroHyp (4q) was the most potent inhibitor of DPP-IV, DPP8 and DPP9, while (4S)-Hyp-(4R)-boroHyp (4o) exhibited the most selectivity for DPP-IV over DPP8 and DPP9.

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