Data/hora: 10/06/2024 11:17:40

Provedor de dados: 	Brazilian Journal of Medical and Biological Research	
País: 	Brazil	
Título: 	Target-directed catalytic metallodrugs	
Autores: 	Joyner,J.C.; Cowan,J.A.	
Data: 	2013-06-01	
Ano: 	2013	
Palavras-chave: 	Catalytic metallodrug; Artificial nuclease; Ribonuclease mimic; Artificial protease; HIV; Angiotensin converting enzyme.	
Resumo: 	Most drugs function by binding reversibly to specific biological targets, and therapeutic effects generally require saturation of these targets. One means of decreasing required drug concentrations is incorporation of reactive metal centers that elicit irreversible modification of targets. A common approach has been the design of artificial proteases/nucleases containing metal centers capable of hydrolyzing targeted proteins or nucleic acids. However, these hydrolytic catalysts typically provide relatively low rate constants for target inactivation. Recently, various catalysts were synthesized that use oxidative mechanisms to selectively cleave/inactivate therapeutic targets, including HIV RRE RNA or angiotensin converting enzyme (ACE). These oxidative mechanisms, which typically involve reactive oxygen species (ROS), provide access to comparatively high rate constants for target inactivation. Target-binding affinity, co-reactant selectivity, reduction potential, coordination unsaturation, ROS products (metal-associated vsmetal-dissociated; hydroxyl vs superoxide), and multiple-turnover redox chemistry were studied for each catalyst, and these parameters were related to the efficiency, selectivity, and mechanism(s) of inactivation/cleavage of the corresponding target for each catalyst. Important factors for future oxidative catalyst development are 1) positioning of catalyst reduction potential and redox reactivity to match the physiological environment of use, 2) maintenance of catalyst stability by use of chelates with either high denticity or other means of stabilization, such as the square planar geometric stabilization of Ni- and Cu-ATCUN complexes, 3) optimal rate of inactivation of targets relative to the rate of generation of diffusible ROS, 4) targeting and linker domains that afford better control of catalyst orientation, and 5) general bio-availability and drug delivery requirements.	
Tipo: 	Info:eu-repo/semantics/article	
Idioma: 	Inglês	
Identificador: 	http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000600465	
Editor: 	Associação Brasileira de Divulgação Científica	
Relação: 	10.1590/1414-431X20133086	
Formato: 	text/html	
Fonte: 	Brazilian Journal of Medical and Biological Research  v.46 n.6 2013	
Fonte: 	info:eu-repo/semantics/openAccess