Inhibition of Pseudomonas aeruginosa elastase and Pseudomonas keratitis using a thiol-based peptide.

Antimicrobial Agents and Chemotherapy
F R BurnsJ T Wells


Pseudomonas aeruginosa elastase is a zinc metalloproteinase which is released during P. aeruginosa infections. Pseudomonas keratitis, which occurs following contact lens-induced corneal trauma, can lead to rapid, liquefactive necrosis of the cornea. This destruction has been attributed to the release of both host-derived enzymes and the bacterial products P. aeruginosa elastase, alkaline protease, exotoxin A, and lipopolysaccharide endotoxin. A synthetic metalloproteinase inhibitor, HSCH2 (DL)CH[CH2CH(CH3)2]CO-Phe-Ala-NH2, which we previously showed to be a potent inhibitor of corneal collagenase and alkali-induced corneal ulceration, was tested as a potential inhibitor of P. aeruginosa elastase. Inhibition constants (Kis) for the resolved diastereomers were determined with the chromogenic substrate furylacryloyl-glycyl-L-leucyl-L-alanine. One isomer had a Ki of 0.3 microM, while the other had a Ki of 0.4 microM. The more potent diastereomer was evaluated in vivo in experimentally induced Pseudomonas keratitis in rabbits. Following inoculation of one cornea of each rabbit, topical treatment with a 1 mM solution of the inhibitor significantly delayed the onset of corneal melting and perforation, as compared with the results for ...Continue Reading


Jan 1, 1986·Journal of Cellular Biochemistry·R D GrayA F Spatola
Feb 1, 1987·Ophthalmology·Elisabeth J CohenC S Clemons
Feb 1, 1987·Archives of Ophthalmology·J A SeedorD S Guthrie
Nov 1, 1972·Archives of Ophthalmology·Peter R Laibson
Jul 26, 1968·Biochemical and Biophysical Research Communications·J Feder
Oct 1, 1983·Archives of Ophthalmology·G Hassman, J Sugar
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN


May 1, 1994·Developmental Dynamics : an Official Publication of the American Association of Anatomists·J B SheffieldE Dehlinger
Nov 25, 2003·Medical Microbiology and Immunology·Mary E MarquartRichard J O'Callaghan
Apr 15, 2014·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Kazuki TajimaHiroshi Goto
Jan 26, 2016·Journal of Medicinal Chemistry·Stefanie WagnerAlexander Titz
Sep 6, 1994·Annals of the New York Academy of Sciences·R D Gray, C A Paterson
Jan 21, 2009·Chemical Biology & Drug Design·Olayiwola A Adekoya, Ingebrigt Sylte
Dec 27, 2005·Journal of Structural Biology·Olayiwola A AdekoyaIngebrigt Sylte
Dec 4, 2004·Biological Chemistry·Koki Matsumoto
Sep 19, 2003·American Journal of Veterinary Research·Franck J OllivierGregory S Schultz
Aug 20, 2019·Journal of Biomolecular Structure & Dynamics·Takuya EzawaNoriyuki Kurita
Jun 3, 2017·Frontiers in Cellular and Infection Microbiology·Jaya D ChidambaramMatthew J Burton
Mar 7, 2021·Drug Discovery Today·Martin J Everett, David T Davies
Oct 22, 1998·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·M A AvidanoG S Schultz

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