title: Boro-norleucine as a P1 residue for the design of selective and potent DPP7 inhibitors.
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.
authors.affiliation: ActivX Biosciences, 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA. kevins@activx.com
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Shreder
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Wong
authors.forename: Sergio
authors.initials: S
authors.lastname: Corral
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Yu
authors.forename: David T
authors.initials: DT
authors.lastname: Winn
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.forename: Tyzoon
authors.initials: T
authors.lastname: Nomanbhoy
authors.forename: Senaiet
authors.initials: S
authors.lastname: Alemayehu
authors.forename: Stacy R
authors.initials: SR
authors.lastname: Fuller
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Rosenblum
authors.forename: John W
authors.initials: JW
authors.lastname: Kozarich
mesh_terms: D001897:Boronic Acids; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D009646:Norleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D001897:Boronic Acids; D004151:Dipeptides; D009646:Norleucine; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II