Τίτλος:
Phosphinic peptides as potent inhibitors of zinc-metalloproteases
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The development of transition-state analogs is a major objective in enzymology, not only for developing potent inhibitors of enzymes but also for dissecting enzyme catalytic mechanisms. Phosphinic peptides, which share closed structural similarities with the transition-state of peptide substrate upon hydrolysis, have thus been considered for identifying potent inhibitors of proteases. Focusing on the zinc-proteases family, this review presents the most important synthetic efforts performed to obtain the desired compounds. Crystal structures of the phosphinic peptides in interaction with their zinc-protease targets are reported to illustrate the structural features which may explain the potency of these compounds and how they contribute to uncover key enzyme catalytic residues. Based on a remarkable metabolic stability, phosphinic peptides can be used to probe the in vivo function of zinc-proteases. Progress on chemistry and better understanding on the functional roles of zinc-proteases should allow transferring these compounds from shelf to clinic. © Springer International Publishing Switzerland 2014.
Συγγραφείς:
Georgiadis, D.
Dive, V.
Περιοδικό:
Topics in Current Chemistry
Λέξεις-κλειδιά:
metalloproteinase; peptide; phosphinic acid derivative; proteinase inhibitor; zinc, animal; antagonists and inhibitors; Bacillus; chemical structure; chemistry; enzyme active site; enzymology; human; Plasmodium falciparum; protein secondary structure; protein tertiary structure; structure activity relation; synthesis; X ray crystallography, Animals; Bacillus; Catalytic Domain; Crystallography, X-Ray; Humans; Metalloproteases; Models, Molecular; Peptides; Phosphinic Acids; Plasmodium falciparum; Protease Inhibitors; Protein Structure, Secondary; Protein Structure, Tertiary; Structure-Activity Relationship; Zinc
DOI:
10.1007/128_2014_571
