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) α-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 IC 50 value of 480 pM.