Open AccessSpecific inhibition of endopeptidase 24.16 by dipeptides
Author(s) -
DAUCH Pascale,
VINCENT JeanPierre,
CHECLER Frédéric
Publication year - 1991
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1991.tb16372.x
Subject(s) - endopeptidase , neprilysin , chemistry , prolyl endopeptidase , neurotensin , aminopeptidase , biochemistry , enzyme , exopeptidase , carboxypeptidase , enkephalinase , enzyme inhibitor , leucine , enkephalin , neuropeptide , amino acid , receptor , opioid
The inhibitory effect of various dipeptides on the neurotensin‐degrading metallopeptidase, endopeptidase 24.16, was examined. These dipeptides mimick the Pro10‐Tyr11 bond of neurotensin that is hydrolyzed by endopeptidase 24.16. Among a series of Pro‐Xaa dipeptides, the most potent inhibitory effect was elicited by Pro‐Ile ( K i ∼ 90 μM) with Pro‐Ile > Pro‐Met > Pro‐Phe. All the Xaa‐Tyr dipeptides were unable to inhibit endopeptidase 24.16. The effect of Pro‐Ile on several purified peptidases was assessed by means of fluorigenic assays and HPLC analysis. A 5 mM concentration of Pro‐Ile does not inhibit endopeptidase 24.11, endopeptidase 24.15, angiotensin‐converting enzyme, proline endopeptidase, trypsin, leucine aminopeptidase, pyroglutamyl aminopeptidase I and carboxypeptidase B. The only enzyme that was affected by Pro‐Ile was carboxypeptidase A, although it was with a 50‐fold lower potency ( K i ∼ 5 mM) than for endopeptidase 24.16. By means of flurimetric substrates with a series of hydrolysing activities, we demonstrate that Pro‐Ile can be used as a specific inhibitor of endopeptidase 24.16, even in a complex mixture of peptidase activities such as found in whole rat brain homogenate.