title: 4-Substituted boro-proline dipeptides: synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities.
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.
authors.affiliation: Tufts University School of Medicine, Department of Biochemistry, 136 Harrison Ave., Boston, MA 02111, United States.
authors.forename: Wengen
authors.initials: W
authors.lastname: Wu
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Liu
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Milo
authors.forename: Ying
authors.initials: Y
authors.lastname: Shu
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Youhua
authors.initials: Y
authors.lastname: Li
authors.forename: Iwona
authors.initials: I
authors.lastname: Woznica
authors.forename: Gengli
authors.initials: G
authors.lastname: Yu
authors.forename: David G
authors.initials: DG
authors.lastname: Sanford
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Poplawski
authors.forename: Beth A
authors.initials: BA
authors.lastname: Connolly
authors.forename: James L
authors.initials: JL
authors.lastname: Sudmeier
authors.forename: William W
authors.initials: WW
authors.lastname: Bachovchin
authors.forename: Jack H
authors.initials: JH
authors.lastname: Lai
mesh_terms: D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D011392:Proline / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001897:Boronic Acids; D004151:Dipeptides; D011392:Proline; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases