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Boro-norleucine as a P1 residue for the design of selective and potent DPP7 inhibitors

Authors :
John W. Kozarich
Melissa S. Wong
David T. Winn
Tyzoon K. Nomanbhoy
Stacy R. Fuller
Jonathan S. Rosenblum
Kevin R. Shreder
Min Wu
Yi Hu
Senaiet Alemayehu
Zhizhou Yu
Sergio Corral
Source :
Bioorganicmedicinal chemistry letters. 15(19)
Publication Year :
2005

Abstract

Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino acids in the P2 position and boro-norleucine (boro-Nle) in the P1 position were synthesized. Relative to boro-proline, boro-Nle as a P1 residue was shown able to significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g) proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value of 480 pM.

Details

ISSN :
0960894X
Volume :
15
Issue :
19
Database :
OpenAIRE
Journal :
Bioorganicmedicinal chemistry letters
Accession number :
edsair.doi.dedup.....aea2d11dfa8f1be80ee25e269573224e