Mono-N-acyl-2,6-diaminopimelic acid derivatives: Analysis by electromigration and spectroscopic methods and examination of enzyme inhibitory activity

0435634 - ÚOCHB 2015 RIV US eng J - Journal Article
Hlaváček, Jan - Vítovcová, M. - Sázelová, Petra - Pícha, Jan - Vaněk, Václav - Buděšínský, Miloš - Jiráček, Jiří - Gillner, D. M. - Holz, R. C. - Mikšík, Ivan - Kašička, Václav
Mono-N-acyl-2,6-diaminopimelic acid derivatives: Analysis by electromigration and spectroscopic methods and examination of enzyme inhibitory activity.
Analytical Biochemistry. Roč. 467, Dec 15 (2014), s. 4-13. ISSN 0003-2697. E-ISSN 1096-0309
R&D Projects: GA ČR(CZ) GAP206/12/0453; GA ČR(CZ) GA13-17224S; GA AV ČR IAA400550614
Institutional support: RVO:61388963 ; RVO:67985823
Keywords : 2,6-diaminopimelic acid derivatives * capillary zone electrophoresis * micellar electrokinetic chromatography * enzyme inhibition
Subject RIV: CB - Analytical Chemistry, Separation
Impact factor: 2.219, year: 2014

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 60 mM 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.
Permanent Link: http://hdl.handle.net/11104/0239682