title: Mono-N-acyl-2,6-diaminopimelic acid derivatives: analysis by electromigration and spectroscopic methods and examination of enzyme inhibitory activity.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hlaváček
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic.
authors.forename: Miloslava
authors.initials: M
authors.lastname: Vítovcová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Sázelová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Pícha
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic.
authors.forename: Václav
authors.initials: V
authors.lastname: Vaněk
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic.
authors.forename: Miloš
authors.initials: M
authors.lastname: Buděšínský
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Jiráček
authors.affiliation: Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL 60626, USA; Department of Chemistry, Silesian University of Technology, 44-100 Gliwice, Poland.
authors.forename: Danuta M
authors.initials: DM
authors.lastname: Gillner
authors.affiliation: Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL 60626, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Holz
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Mikšík
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic. Electronic address: kasicka@uochb.cas.cz.
authors.forename: Václav
authors.initials: V
authors.lastname: Kašička
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D003960:Diaminopimelic Acid / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D006193:Haemophilus influenzae / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D013055:Spectrophotometry, Infrared / Q000379:methods*
chemical_list: D000581:Amidohydrolases; D003960:Diaminopimelic Acid; D004791:Enzyme Inhibitors; C018732:N-acetylornithine deacetylase; C054685:N-succinyl-l,l-diaminopimelic acid desuccinylase
keywords: 2,6-Diaminopimelic acid derivatives; Capillary zone electrophoresis; Enzyme inhibition; IR spectroscopy; Micellar electrokinetic chromatography; NMR spectroscopy