Prevention of peroxynitrite-dependent damage by carnosine and related sulphonamido pseudodipeptides.
The naturally occurring dipeptides carnosine and anserine have been proposed to act as antioxidants in vivo. We investigated whether these compounds can act as protective agents able to counteract peroxynitrite-dependent reactions. The results showed that the dipeptides efficiently protect tyrosine against nitration, alpha1-antiproteinase against inactivation and human low-density lipoprotein against modification by peroxynitrite. Carnosine exerts its protective effect at concentrations similar to those found in human tissues. In addition, some synthetic pseudodipeptides, stucturally related to carnosine but stable to hydrolytic enzymes, possess protective properties against peroxynitrite-dependent damage similar to the natural dipeptides. These pseudodipeptides may represent stable mimics of the biologically active carnosine suitable for pharmacological applications.
Fontana
M
M
Dipartimento di Scienze Biochimiche, Università di Roma La Sapienza, and Centro di Biologia Molecolare, CNR, Rome, Italy. mario.fontana@uniroma1.it
Pinnen
F
F
Lucente
G
G
Pecci
L
L
D000861:Anserine / Q000737:chemistry / Q000378:metabolism*; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D002336:Carnosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000975:Antioxidants; D008077:Lipoproteins, LDL; D000515:alpha 1-Antitrypsin; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D002336:Carnosine; D000861:Anserine