Thirteen mono-N-acyl derivatives of 2,6-diaminopimelic acid (DAP)-new potential inhibitors of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18)-were analyzed and characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopies and two capillary electromigration methods: capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC). Structural features of DAP derivatives were characterized by IR and NMR spectroscopies, whereas CZE and MEKC were applied to evaluate their purity and to investigate their electromigration properties. Effective electrophoretic mobilities of these compounds were determined by CZE in acidic and alkaline background electrolytes (BGEs) and by MEKC in acidic and alkaline BGEs containing a pseudostationary phase of anionic detergent sodium dodecyl sulfate (SDS) or cationic detergent cetyltrimethylammonium bromide (CTAB). The best separation of DAP derivatives, including diastereomers of some of them, was achieved by MEKC in an acidic BGE (500 mM acetic acid [pH 2.54] and 60mM SDS). All DAP derivatives were examined for their ability to inhibit catalytic activity of DapE from Haemophilus influenzae (HiDapE) and ArgE from Escherichia coli (EcArgE). None of these DAP derivatives worked as an effective inhibitor of HiDapE, but one derivative-N-fumaryl, Me-ester-DAP-was found to be a moderate inhibitor of EcArgE, thereby providing a promising lead structure for further studies on ArgE inhibitors.

• Klíčová slova
• 2,6-Diaminopimelic acid derivatives, Capillary zone electrophoresis, Enzyme inhibition, IR spectroscopy, Micellar electrokinetic chromatography, NMR spectroscopy,
• MeSH
• amidohydrolasy antagonisté a inhibitory   MeSH
• elektroforéza kapilární metody   MeSH
• Escherichia coli enzymologie   MeSH
• Haemophilus influenzae enzymologie   MeSH
• inhibitory enzymů chemie   farmakologie   MeSH
• kyselina diaminopimelová chemie   MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• spektrofotometrie infračervená metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• amidohydrolasy MeSH
• inhibitory enzymů MeSH
• kyselina diaminopimelová MeSH
• N-acetylornithine deacetylase MeSH Prohlížeč
• succinyldiaminopimelate desuccinylase MeSH Prohlížeč

The search for potential inhibitors that target so far unexplored bacterial enzyme mono-N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) has stimulated a development of methodology for quick and efficient preparation of mono-N-acylated 2,6-diaminopimelic acid (DAP) derivatives bearing the different carboxyl groups or lipophilic moieties on their amino group.

• MeSH
• acylace MeSH
• biomimetické materiály chemická syntéza   chemie   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• kyselina diaminopimelová analogy a deriváty   chemická syntéza   chemie   MeSH
• metabolické sítě a dráhy MeSH
• molekulární modely MeSH
• sukcináty chemická syntéza   chemie   MeSH
• sukcinyldiaminopimeláttransaminasa antagonisté a inhibitory   metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyselina diaminopimelová MeSH
• sukcináty MeSH
• sukcinyldiaminopimeláttransaminasa MeSH