Τίτλος:
Phosphinic pseudo-tripeptides as potent inhibitors of matrix metalloproteinases: A structure-activity study
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Several phosphinic pseudo-tripeptides of general formula R-XaaΨ(PO2- CH2)Xaa'-Yaa'-NH2 were synthesized and evaluated for their in vitro activities to inhibit stromelysin-3, gelatinases A and B, membrane type-1 matrix metalloproteinase, collagenases 1 and 2, and matrilysin. With the exception of collagenase-1 and matrilysin, phosphinic pseudo-tripeptides behave as highly potent inhibitors of matrix metalloproteinases, provided they contain in P1' position an unusual long aryl-alkyl substituent. Study of structure-activity relationships regarding the influence of the R and Xaa' substituents in this series may contribute to the design of inhibitors able to block only a few members of the matrix metalloproteinase family.
Συγγραφείς:
Vassiliou, S.
Mucha, A.
Cuniasse, P.
Georgiadis, D.
Lucet-Levannier, K.
Beau, F.
Kannan, R.
Murphy, G.
Knäuper, V.
Rio, M.-C.
Basset, P.
Yiotakis, A.
Dive, V.
Περιοδικό:
Journal of Medicinal Chemistry
Λέξεις-κλειδιά:
collagenase; gelatinase a; gelatinase b; matrilysin; matrix metalloproteinase; matrix metalloproteinase inhibitor; phosphinic acid derivative; phosphinic pseudotripeptide; stromelysin; tripeptide; unclassified drug, article; drug structure; drug synthesis; enzyme inhibition; in vitro study; reaction analysis; structure activity relation, Kinetics; Magnetic Resonance Spectroscopy; Metalloendopeptidases; Oligopeptides; Phosphines; Protease Inhibitors; Structure-Activity Relationship