Kinetic evaluation of a metalated diglycine conjugate as a functional mimetic of phosphate ester hydrolase.
The crucial role of phosphate ester hydrolysis in various biological processes has spurred vigorous research activities to understand mechanisms of phosphate ester hydrolysis and to develop model systems that assist the above-mentioned reaction in a catalytic fashion. In the present study, we describe a novel, metalated peptide conjugate 4 possessing phosphate ester hydrolyzing activity against a phosphate monoester, diester, and a RNA chemical model. The design of conjugate 4 is inspired by the ATCUN binding tripeptide motif of serum albumin and involves tethering of two diglycine units by a flexible 1,3-diaminopropane linker. Detailed kinetic investigations of phosphate ester hydrolysis using model substrates and efforts to decipher underlying mechanisms are presented.
Madhavaiah
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Department of Chemistry, Indian Institute of Technology-Kanpur, Kanpur-208016 (UP), India.
Verma
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D020816:Amino Acid Motifs; D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006033:Glycylglycine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008353:Mannitol / Q000494:pharmacology; D018716:Molecular Mimicry; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D012997:Solvents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D012997:Solvents; D006033:Glycylglycine; D008353:Mannitol; D010744:Phosphoric Monoester Hydrolases; D010727:Phosphoric Diester Hydrolases