Replacements for lysine in l-seryl- l-lysyl dipeptide amide inhibitors of candida albicans myristoyl-CoA:protein N-myristoyltransferase

A survey of potential cyclic and acyclic lysine replacements in known l-seryl- l-lysyl dipeptide inhibitors of C. albicans NMT identified the thioether 16 and glycinamide 18 as submicromolar inhibitors of C. albicans NMT, which retained good selectivity over the human enzyme. All of the heterocyclic...

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Published inBioorganic & medicinal chemistry letters Vol. 7; no. 3; pp. 379 - 382
Main Authors Brown, David L., Devadas, Balekudru, Lu, Hwang-Fun, Nagarajan, Srinivasan, Zupec, Mark E., Freeman, Sandra K., McWherter, Charles A., Getman, Daniel P., Sikorski, James A.
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 04.02.1997
Elsevier
Subjects
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
Biological and medical sciences
Medical sciences
Pharmacology. Drug treatments
Candida albicans
Imidazole derivatives
Enzyme
Aminoamide
Transferases
Enzyme inhibitor
Aminosulfide
In vitro
Fungi
Antifungal agent
Chemical modification
Structure activity relation
Dipeptides
Peptide synthesis
Fungi Imperfecti
Chemical synthesis
Thallophyta
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Summary:A survey of potential cyclic and acyclic lysine replacements in known l-seryl- l-lysyl dipeptide inhibitors of C. albicans NMT identified the thioether 16 and glycinamide 18 as submicromolar inhibitors of C. albicans NMT, which retained good selectivity over the human enzyme. All of the heterocyclic lysine mimetics that were examined exhibited dramatically weaker affinity with the fungal enzyme. A potent and selective peptidomimetic inhibitor 18 has been identified where the basic lysine side chain has been replaced with a less basic glycinamide.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(97)00030-9