Inhibition of dipeptidyl peptidase IV (DPP IV) by 2-(2-amino-1-fluoro-propylidene)-cyclopentanecarbonitrile, a fluoroolefin containing peptidomimetic.
Novel, potent inhibitors of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5, CD26), containing the fluoroolefin peptide isostere psi [CFz.dbnd6;C], have been prepared via the intermediacy of the Peterson fluoroolefination reaction. The nitrile containing inhibitors were found to inhibit dipeptidyl peptidase IV competitively with K(i) values for the l-3 and u-3 inhibitors of 7.69 and 6.03 microM, respectively. In contrast to earlier reported fluoroolefin containing inhibitors, the nitriles underwent no detectable degradation at pH 7.6 under buffered conditions.
Zhao
Kake
K
Department of Chemistry, University at Albany, Albany, NY 12222, USA.
Lim
Dong Sung
DS
Funaki
Takashi
T
Welch
John T
JT
D001667:Binding, Competitive; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004355:Drug Stability; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009570:Nitriles / Q000737:chemistry* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism
D009570:Nitriles; D010455:Peptides; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4