Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals:
An Alternative Model for Covalent Modification of Proteins

J 1998

Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals: An Alternative Model for Covalent Modification of Proteins

BAKER, Andrew, Lukáš ŽÍDEK, Don WIESLER a Milos NOVOTNY

Základní údaje

Originální název

Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals: An Alternative Model for Covalent Modification of Proteins

Autoři

BAKER, Andrew, Lukáš ŽÍDEK, Don WIESLER a Milos NOVOTNY

Vydání

Chemical Research in Toxicology, Washington, DC (USA), American Chemical Society, 1998, 08993228X

Další údaje

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

LOW-DENSITY-LIPOPROTEIN; MASS-SPECTROMETRY; ADDUCTS; PEROXIDATION; ALDEHYDES; HISTIDINE; GLYCINE; LYSINE

Štítky

ADDUCTS, ALDEHYDES, GLYCINE, HISTIDINE, LOW-DENSITY-LIPOPROTEIN, LYSINE, MASS-SPECTROMETRY, PEROXIDATION

Změněno: 21. 5. 2001 08:50, prof. Mgr. Lukáš Žídek, Ph.D.

Anotace

V originále

Among the various reactions of lipid peroxidation products with proteins, 2-alkenals have been shown to react extensively with the epsilon-amino group of lysine residues [Zidek et al. (1997) Chem. Res. Toxicol. 10, 702-710]. To obtain additional information about the kinetic and mechanistic aspects of this modification, a model peptide (N-acetylglycyllysine O-methyl ester) was reacted with 2-hexenal. The reaction products were characterized through a combination of NMR and MS techniques. The structural elucidation efforts have shown the formation of pyridinium salts through the reaction of two or more alkenals with one amino group. Kinetic data were obtained using a continuous infusion of the reaction mixture into an electrospray ionization mass spectrometer. A mechanism is proposed that; offers an alternative model for the formation of stable protein cross-links. The reaction progresses through a Schiff base intermediate to form a dihydropyridine species which can be alternatively reduced to form various 3,4- or 2,5-substituted pyridinium species or react with another Schiff base to form a trialkyl-substituted pyridinium structure. The stoichiometry of this structure (aldehyde/amine) is 3:2, in contrast to the widely accepted 1:2. Therefore, it represents another possible crosslinking mechanism for bifunctional products of lipid peroxidation.

Citovat

BAKER, Andrew, Lukáš ŽÍDEK, Don WIESLER a Milos NOVOTNY. Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals: An Alternative Model for Covalent Modification of Proteins. Chemical Research in Toxicology. Washington, DC (USA): American Chemical Society, 1998, roč. 11, č. 7, s. 730-740. ISSN 08993228X.

@article{205691,
   author = {Baker, Andrew and Žídek, Lukáš and Wiesler, Don and Novotny, Milos},
   article_location = {Washington, DC (USA)},
   article_number = {7},
   keywords = {LOW-DENSITY-LIPOPROTEIN; MASS-SPECTROMETRY; ADDUCTS; PEROXIDATION; ALDEHYDES;
HISTIDINE; GLYCINE; LYSINE},
   issn = {08993228X},
   journal = {Chemical Research in Toxicology},
   title = {Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals: An Alternative Model for Covalent Modification of Proteins},
   volume = {11},
   year = {1998}
}

TY  - JOUR
ID  - 205691
AU  - Baker, Andrew - Žídek, Lukáš - Wiesler, Don - Novotny, Milos
PY  - 1998
TI  - Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals: An Alternative Model for Covalent Modification of Proteins
JF  - Chemical Research in Toxicology
VL  - 11
IS  - 7
SP  - 730
EP  - 730
PB  - American Chemical Society
SN  - 08993228X
KW  - LOW-DENSITY-LIPOPROTEIN
KW  - MASS-SPECTROMETRY
KW  - ADDUCTS
KW  - PEROXIDATION
KW  - ALDEHYDES
KW  - HISTIDINE
KW  - GLYCINE
KW  - LYSINE
N2  - Among the various reactions of lipid peroxidation products with proteins, 2-alkenals have been shown to react extensively with the epsilon-amino group of lysine residues [Zidek et al. (1997) Chem. Res. Toxicol. 10, 702-710]. To obtain additional information about the kinetic and mechanistic aspects of this modification, a model peptide (N-acetylglycyllysine O-methyl ester) was reacted with 2-hexenal. The reaction products were characterized through a combination of NMR and MS techniques. The structural elucidation efforts have shown the formation of pyridinium salts through the reaction of two or more alkenals with one amino group. Kinetic data were obtained using a continuous infusion of the reaction mixture into an electrospray ionization mass spectrometer. A mechanism is proposed that; offers an alternative model for the formation of stable protein cross-links. The reaction progresses through a Schiff base intermediate to form a dihydropyridine species which can be alternatively reduced to form various 3,4- or 2,5-substituted pyridinium species or react with another Schiff base to form a trialkyl-substituted pyridinium structure. The stoichiometry of this structure (aldehyde/amine) is 3:2, in contrast to the widely accepted 1:2. Therefore, it represents another possible crosslinking mechanism for bifunctional products of lipid peroxidation.
ER  -

BAKER, Andrew, Lukáš ŽÍDEK, Don WIESLER a Milos NOVOTNY. Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals: An Alternative Model for Covalent Modification of Proteins. \textit{Chemical Research in Toxicology}. Washington, DC (USA): American Chemical Society, 1998, roč.~11, č.~7, s.~730-740. ISSN~08993228X.

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