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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Boronic Acids / chemical synthesis
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Boronic Acids / chemistry*
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Boronic Acids / pharmacology*
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Diabetes Mellitus, Type 2 / drug therapy
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Diabetes Mellitus, Type 2 / enzymology
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Dipeptides / chemical synthesis
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Dipeptides / chemistry*
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Dipeptides / pharmacology*
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism
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Humans
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Inhibitory Concentration 50
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Proline / chemical synthesis
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Proline / chemistry*
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Proline / pharmacology*
Substances
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Boronic Acids
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Dipeptides
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Proline
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases