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Mono-N-acyl-2,6-diaminopimelic Acid Derivatives: Analysis by Electromigration and Spectroscopic Methods and Examination of Enzyme Inhibitory Activity
Analytical Biochemistry
  • Jan Hlaváček, Academy of Sciences of the Czech Republic
  • Miloslava Vítovcová, Academy of Sciences of the Czech Republic
  • Petra Sázelová, Academy of Sciences of the Czech Republic
  • Jan Pícha, Academy of Sciences of the Czech Republic
  • Václav Vaněk, Academy of Sciences of the Czech Republic
  • Miloš Buděšínský, Academy of Sciences of the Czech Republic
  • Jiří Jiráček, Academy of Sciences of the Czech Republic
  • Danuta M. Gillner, Loyola University Chicago
  • Richard C. Holz, Marquette University
  • Ivan Mikšík, Academy of Sciences of the Czech Republic
  • Václav Kašička, Academy of Sciences of the Czech Republic
Document Type
Article
Publication Date
12-15-2014
Disciplines
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 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.
Comments

Analytical Biochemistry, Vol. 467 (December 15, 2014): 4-13. DOI.

Richard C. Holz was affiliated with Loyola University Chicago at the time of publication.

Citation Information
Jan Hlaváček, Miloslava Vítovcová, Petra Sázelová, Jan Pícha, et al.. "Mono-N-acyl-2,6-diaminopimelic Acid Derivatives: Analysis by Electromigration and Spectroscopic Methods and Examination of Enzyme Inhibitory Activity" Analytical Biochemistry (2014) ISSN: 0003-2697
Available at: http://works.bepress.com/richard_holz/82/