RESUMO
We report construction of a bis-pentapeptide conjugate 4 containing truncated pentapeptide sequence from prion octarepeats. Its copper-laden derivative 5 demonstrated a propensity for aggregate formation, which was studied by atomic force microscopy. Oxidative biochemical transformations catalyzed by 5 were evaluated by nucleic acid cleavage and by neurotransmitter oxidation, in the presence of external co-oxidants. Preliminary mechanistic analysis provides a hint for the involvement of reactive oxygen species in such transformations.
Assuntos
Cobre/química , Oligopeptídeos/química , Oligopeptídeos/síntese química , Príons/química , Príons/síntese química , Motivos de Aminoácidos/fisiologia , Catálise , Conformação Molecular , Ácidos Nucleicos/química , Oxirredução , Espécies Reativas de Oxigênio/química , Sequências Repetitivas de Aminoácidos/fisiologia , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Lipophilic hexaporphyrin free-base and copper-metalated assemblies supported on a Sn6O6 core have been synthesized and characterized. The nuclease activity of the copper derivative has been studied.
RESUMO
A series of copper-metalated, water-soluble bis-diglycine conjugates were synthesized and characterized through spectroscopic methods. These conjugates were evaluated for the cleavage of phosphodiester substrates, supercoiled plasmid relaxation in the presence of co-oxidants, and for the oxidation of a diphenolic substrate, 2,6-dimethoxyphenol. Appreciable rate enhancements were observed for these reactions and the oxidative nucleolytic cleavage activity and phenol oxidative coupling was presumably manifested via formation of reactive oxygen species.
Assuntos
Cobre/química , Glicilglicina/análogos & derivados , Glicilglicina/síntese química , Domínio Catalítico/efeitos dos fármacos , Domínio Catalítico/fisiologia , Cobre/metabolismo , Glicilglicina/metabolismo , Estrutura Molecular , OxirreduçãoRESUMO
Pendant pyrazolylcyclophosphazene containing hybrid cross-linked polymer (CPPL) has been utilized for binding Zn(II). The metalated polymer (CPPL-Zn) has been found to be very effective catalyst for the hydrolysis of a RNA model phosphodiester substrate [2-(hydroxypropyl)-p-nitrophenyl phosphate, hNPP]. In addition, CPPL-Zn also cleaved supercoiled plasmid DNA pBR322 thus providing a novel structural motif of inorganic-organic hybrid polymers as synthetic nucleases.
Assuntos
Metais/farmacocinética , Fosfatos/farmacocinética , Plasmídeos/farmacocinética , Polímeros/farmacocinética , Catálise/efeitos dos fármacos , Ésteres , Hidrólise/efeitos dos fármacos , Metais/química , Fosfatos/química , Plasmídeos/química , Polímeros/químicaRESUMO
A novel bis scaffold containing a pentapeptide PHGGG, derived from the prion octarepeat, forms fibrils of nanometric dimensions, thus indicating that certain segments in the unstructured region of the prion protein may facilitate an initial fibrillation event.
Assuntos
Peptídeos/química , Peptídeos/síntese química , Príons/química , Estrutura MolecularRESUMO
Relaxation of supercoiled plasmid by uranyl ions impregnated on a adenylated polymeric support has been observed in the presence of visible light and sunlight. This insoluble polymer support permits facile reusability of the catalytic system and it failed to cleave lysozyme under the conditions employed for plasmid modification.
Assuntos
Adenina/química , DNA Super-Helicoidal/química , Desoxirribonucleases/química , Plasmídeos/química , Polímeros/química , Urânio/química , Catálise , DNA Super-Helicoidal/efeitos dos fármacos , DNA Super-Helicoidal/efeitos da radiação , Desoxirribonucleases/farmacologia , Sequestradores de Radicais Livres/farmacologia , Luz , Conformação de Ácido Nucleico , Fotólise , Plasmídeos/efeitos dos fármacos , Plasmídeos/efeitos da radiação , Luz SolarRESUMO
This paper reports synthesis and plasmid modification activities of a new class of insoluble copper-metalated diglycine conjugates, containing aliphatic linkers of varying length. Besides providing significant rate enhancement for model phosphate ester cleavage, these constructs also displayed efficient supercoiled plasmid scission, in the absence of co-oxidants, under heterogeneous catalytic conditions.
Assuntos
Cobre/química , Glicilglicina/análogos & derivados , Glicilglicina/farmacologia , Plasmídeos/química , Catálise , Reagentes de Ligações Cruzadas/química , DNA Super-Helicoidal/química , Sequestradores de Radicais Livres/química , Glicilglicina/química , Hidrólise , Cinética , Nitrofenóis/química , Conformação de Ácido Nucleico , Compostos Organofosforados/química , SolubilidadeRESUMO
The crucial role of phosphate ester hydrolysis in various biological processes has spurred vigorous research activities to understand mechanisms of phosphate ester hydrolysis and to develop model systems that assist the above-mentioned reaction in a catalytic fashion. In the present study, we describe a novel, metalated peptide conjugate 4 possessing phosphate ester hydrolyzing activity against a phosphate monoester, diester, and a RNA chemical model. The design of conjugate 4 is inspired by the ATCUN binding tripeptide motif of serum albumin and involves tethering of two diglycine units by a flexible 1,3-diaminopropane linker. Detailed kinetic investigations of phosphate ester hydrolysis using model substrates and efforts to decipher underlying mechanisms are presented.
