@article{3026835,
    title = "Phosphinic peptides as potent inhibitors of zinc-metalloproteases",
    author = "Georgiadis, D. and Dive, V.",
    journal = "Topics in Current Chemistry",
    year = "2014",
    volume = "360",
    publisher = "Springer-Verlag",
    issn = "2365-0869, 2364-8961",
    doi = "10.1007/128_2014_571",
    keywords = "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",
    abstract = "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."
}