6533b853fe1ef96bd12accf4
RESEARCH PRODUCT
N-Benzyl Residues as the P1′ Substituents in Phosphorus-Containing Extended Transition State Analog Inhibitors of Metalloaminopeptidases
Małgorzata PawełczakKamila JaniszewskaPaweł KafarskiMichał TalmaArtur MuchaBartosz Oszywasubject
Stereochemistryenzyme inhibitorsPharmaceutical Scienceorganophosphorus compoundsPhosphinateArticleAnalytical Chemistrylcsh:QD241-44103 medical and health scienceschemistry.chemical_compoundHydrolysis0302 clinical medicinelcsh:Organic chemistryTransition state analogpeptide analogsDrug DiscoveryCarboxylatePhysical and Theoretical ChemistryMethylene030304 developmental biologychemistry.chemical_classification0303 health sciencesDipeptideOrganic Chemistryligand-enzyme interactionsmolecular modeling and dockingEnzymechemistryChemistry (miscellaneous)030220 oncology & carcinogenesisMolecular MedicineLeucinedescription
Peptidyl enzyme inhibitors containing an internal aminomethylphosphinic bond system (P(O)(OH)-CH2-NH) can be termed extended transition state analogs by similarity to the corresponding phosphonamidates (P(O)(OH)-NH). Phosphonamidate pseudopeptides are broadly recognized as competitive mechanism-based inhibitors of metalloenzymes, mainly hydrolases. Their practical use is, however, limited by hydrolytic instability, which is particularly restricting for dipeptide analogs. Extension of phosphonamidates by addition of the methylene group produces a P-C-N system fully resistant in water conditions. In the current work, we present a versatile synthetic approach to such modified dipeptides, based on the three-component phospha-Mannich condensation of phosphinic acids, formaldehyde, and N-benzylglycines. The last-mentioned component allowed for simple and versatile introduction of functionalized P1&prime
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-09-01 | Molecules |