PMID: 9531473Jun 11, 1998Paper

Phosphinic peptides, the first potent inhibitors of astacin, behave as extremely slow-binding inhibitors

The Biochemical Journal
I YiallourosV Dive

Abstract

A series of phosphinic pseudo-peptides varying in length and composition have been designed as inhibitors of the crayfish zinc endopeptidase astacin, the prototype of the astacin family and of the metzincin superfamily of metalloproteinases. The most efficient phosphinic peptide, fluorenylmethyloxycarbonyl-Pro-Lys-PhePsi(PO2CH2)Ala-P ro-Leu-Val, binds to astacin with a Ki value of 42 nM, which is about three orders of magnitude below the corresponding values for previously used hydroxamic acid derivatives. However, the rate constants for association (kon = 96.8 M-1.s-1) and dissociation (koff = 4.1 x 10(-6) s-1) are evidence for the extremely slow binding behaviour of this compound. N-terminally or C-terminally truncated phosphinic analogues of this parent molecule are much less potent, indicating a critical role of the peptide size on the potency. In particular, omission of the N-terminal proline residue leads to a 40-fold increase in Ki which is mostly due to a 75-fold higher koff value. These findings are consistent with the previously solved crystal structure of astacin complexed with one of the phosphinic peptides, benzyloxycarbonyl-Pro-Lys-PhePsi(PO2CH2)Ala-Pro-O-methyl, Ki = 14 microM [Grams, Dive, Yiotakis, Yiallouros, ...Continue Reading

Citations

Dec 3, 2014·Microbial Pathogenesis·Stella CascioferroDomenico Schillaci
Apr 24, 2012·International Journal of Biological Macromolecules·Vishnu Menon, Mala Rao
Jul 29, 2008·Molecular Aspects of Medicine·Athanasios Yiotakis, Vincent Dive
Apr 11, 2017·Journal of Medicinal Chemistry·Manishabrata BhowmickGregg B Fields
Jun 10, 2004·Bioorganic & Medicinal Chemistry·Ryan G KrugerDewey G McCafferty
Apr 16, 2004·Proceedings of the National Academy of Sciences of the United States of America·Akihiro HasegawaMark I Greene
Oct 4, 2000·Journal of Peptide Science : an Official Publication of the European Peptide Society·J Deadman
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·V DiveP Corvol
Mar 15, 2015·Chembiochem : a European Journal of Chemical Biology·Manishabrata BhowmickGregg B Fields
Dec 5, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anna M KnapinskaGregg B Fields
Aug 15, 2003·Organic Letters·Galina V KapustinFelicia A Etzkorn
Aug 4, 2007·Journal of the American Chemical Society·Janelle Lauer-FieldsGregg B Fields
Aug 17, 2005·Biochemistry·Jennifer Madeo, M R Gunner

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.