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Titolo:
Novel 2,5-hexanedione analogues. Substituent-induced control of the protein cross-linking potential and oxidation susceptibility of the resulting primary amine-derived pyrroles
Autore:
Xu, GZ; Singh, MP; Gopal, D; Sayre, LM;
Indirizzi:
Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA Case WesternReserve Univ Cleveland OH USA 44106 Cleveland, OH 44106 USA
Titolo Testata:
CHEMICAL RESEARCH IN TOXICOLOGY
fascicolo: 3, volume: 14, anno: 2001,
pagine: 264 - 274
SICI:
0893-228X(200103)14:3<264:N2ASCO>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-DIKETONE NEUROPATHY; PAAL-KNORR SYNTHESIS; 3,4-DIMETHYL SUBSTITUTION; NEUROFILAMENT TRANSPORT; CYTOSKELETAL PROTEINS; AXONAL SWELLINGS; IN-VITRO; RAT; NEUROTOXICITY; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Sayre, LM Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA Case Western Reserve Univ Cleveland OH USA 44106 , OH 44106 USA
Citazione:
G.Z. Xu et al., "Novel 2,5-hexanedione analogues. Substituent-induced control of the protein cross-linking potential and oxidation susceptibility of the resulting primary amine-derived pyrroles", CHEM RES T, 14(3), 2001, pp. 264-274

Abstract

The neurotoxic gamma -diketone, 2,5-hexanedione (2,5-HD), induces neurofilamentous swellings at prenodal sites in proximal axons as a consequence of pyrrolation of lysine E-amino groups on neurofilament proteins. However, there is disagreement as to whether pyrrole formation and the associated alteration of noncovalent interactions is sufficient to cause neurofilament accumulation, or whether pyrrole autoxidation and subsequent protein-protein cross-linking is an obligatory event. To investigate gamma -diketones that might form pyrroles inert to autoxidative-induced cross-linking, we synthesized 1,1,1-trifluoro-2,5-hexanedione, 3-(trifluoromethyl)-2,5-hexanedione (3-TFMHD), and two 3-(dialkylaminocarbonyl)-2,5-diketones and assessed their rates of pyrrole formation with amines, the oxidation susceptibility of theresulting pyrroles, and the protein cross-linking potential in vitro, relative to those of 3-methyl-2,5-hexanedione. 1,1,1-Trifluoro-2,5-hexanedione does not form pyrroles, but the three 2,5-HD analogues with an electron-withdrawing 3-substituent all rapidly formed pyrroles that were inert to autoxidation. Although 3-TMFHD nonetheless still induced cross-linking of ribonuclease A, by a nonoxidative mechanism independent of the pyrrole, the two 3-(dialkylaninocarbonyl)-2,5-diketones did not exhibit any protein cross-linking. As these two gamma -diketones possess aqueous-organic partitioning properties similar to those of 2,5-HD, they should serve as useful mechanistic probes in further studies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 16:21:20