Biochemical properties of new synthetic carnosine analogues containing the residue of 2,3-diaminopropionic acid: the effect of N-acetylation.
Three novel carnosine analogues 7-9 containing the residue of L(+)2,3-diaminopropionic acid with different degree of N-acetylation instead of beta-alanine have been synthesized and characterized. Comparative analysis of hydrolysis by carnosinase revealed that the mono- and bis-acetylated compounds 8 and 9 are resistant to enzymatic hydrolysis and act as competitive inhibitors of this enzyme. The hydroxyl radical scavenging potential of the three analogues was evaluated by their ability to inhibit iron/H(2)O(2)-induced degradation of deoxyribose. The second-order rate constants of the reaction of compounds 7-9 with hydroxyl radical were almost identical to that of carnosine. These compounds were also found to act as protective agents against peroxynitrite-dependent damage as assessed by their ability to prevent nitration of free tyrosine induced by this species.
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Dipartimento di Scienze del Farmaco, Università degli Studi G. d'Annunzio, 66013 Chieti, Italy.
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Pecci
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D000107:Acetylation; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001671:Biochemistry / Q000379:methods; D002336:Carnosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004150:Dipeptidases / Q000037:antagonists & inhibitors / Q000097:blood; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D017665:Hydroxyl Radical; D018716:Molecular Mimicry; D030421:Peroxynitrous Acid / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000737:chemistry
D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D015091:beta-Alanine; D030421:Peroxynitrous Acid; D017665:Hydroxyl Radical; D014443:Tyrosine; C011757:2,3-diaminopropionic acid; D002336:Carnosine; D004150:Dipeptidases; C019673:aminoacyl-histidine dipeptidase