Regioselective binding of spermine, N¹,N12-bismethylspermine, and N¹,N12-bisethylspermine to tRNA Phe as revealed by 750 MHz ¹H-NMR and its possible correlation with cell cycling and cytotoxicity
Título del documento: Regioselective binding of spermine, N¹,N12-bismethylspermine, and N¹,N12-bisethylspermine to tRNA Phe as revealed by 750 MHz ¹H-NMR and its possible correlation with cell cycling and cytotoxicity
Revista: Journal of the Brazilian Chemical Society
Base de datos: PERIÓDICA
Número de sistema: 000310833
ISSN: 0103-5053
Autors: 1
2

3
Institucions: 1SLIL Biomedical Corporation, Madison, Wisconsin. Estados Unidos de América
2University of Wisconsin-Madison, National Magnetic Resonance Facility, Madison, Wisconsin. Estados Unidos de América
3Roswell Park Cancer Institute, Grace Cancer Drug Center, Buffalo, Nueva York. Estados Unidos de América
Any:
Període: Ago
Volum: 10
Número: 4
Paginació: 334-340
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés The binding of spermine (SPM), N¹,N12-bismethylspermine (BMS) and N¹,N12-bisethylspermine (BES) to tRNA Phe was studied using ¹H-NMR at 750 MHz. The polyamines were enriched in 13C at the 5-CH2 and 8-CH2 residues and the nuclear Overhauser enhancement (NOE) cross peaks connecting the ¹H-NMR resonances of the13C-methylenes and several base paired imino protons of tRNA Phe were obtained using 1D13C-half filteredspectra. It was found that while SPM and BMS bind to the N(3)-H of base pairs T54-m¹A58, U50-A64 and U52-A62, BES binds only to T54-m¹A58 and U50-A64. This regioselectivity in the binding of the three polyamines to tRNA was correlated with their biological effects on cell growth. Using human melanoma cancer cells (MALME-3M), we found that SPM and BMS were without effect and cytostatic, respectively, while BES was distinctly cytotoxic. The latter also affected cell cycling and, at variance with SPM and BMS, lead to a distinctG1/S cell cycle arrest
Resumen en portugués Neste trabalho foi feito o estudo de ligação de espermina (SPM), N¹, N12- bismetilespermina (BMS) e N¹, N12-bisetilespermina (BES) ao tRNAfenusando RMN de¹H a 750 MHz. As poliaminas foram enriquecidas com13C nos resíduos 5-CH2 e 8-CH2, sendo obtidos os picos cruzados por efeito de Overhauser nuclear entre as ressonâncias dos hidrogênios dos metilenos marcados com 13C e vários hidrogênios de grupos imino de pares debases do tRNAfen através de espectros 1D filtrados por13C. Foi encontrado que, enquanto SPM e BMS se ligam ao N(3)-H dos pares de bases T54-m¹A58, U50-A64 e U52-A62, BES liga-se só nos pares T54-m¹A58 e U50-A64. Esta regiosseletividade de ligação das três poliaminas ao tRNA foicorrelacionada com seus efeitos biológicos no crescimento celular. Usando células de câncer de melanoma humano (MALME-3M), foi encontrado que SPM e BMS não tem efeito e é citostático, respectivamente, enquanto que BES é claramente citotóxica. Esta última poliamina também afeta o ciclo celular e, contrário aocomportamento de SPM e BMS, acarreta a uma clara parada do ciclo celular G1 /S
Disciplines Química,
Medicina
Paraules clau: Química farmacéutica,
Oncología,
Poliaminas,
Melanoma,
Espermina,
Resonancia magnética nuclear
Keyword: Chemistry,
Medicine,
Medicinal chemistry,
Oncology,
Polyamines,
Melanoma,
Spermine,
Nuclear magnetic resonance
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