Optimum modification for the highest cytotoxicity of cationized ribonuclease.
J Biochem
; 132(2): 223-8, 2002 Aug.
Article
em En
| MEDLINE
| ID: mdl-12153719
ABSTRACT
Cationization of a protein is considered to be a powerful strategy for internalizing a functional protein into cells. Cationized proteins appear to adsorb to the cell surface by electrostatic interactions, then enter the cell in a receptor- and transporter-independent fashion. Thus, in principle, all cell types appear to take up cationized proteins. Since ribonucleases (RNases) have a latent cytotoxic potential, cationized RNases could be useful cancer chemotherapeutics. In this study, we investigated the effect of the degree of cationization on the cytotoxicity of RNase A by modifying carboxyl groups with ethylenediamine. We found that there is an optimum degree of modification for cytotoxicity, in which 5 to 7 out of 11 carboxyl groups in RNase A are modified, toward MCF-7 and 3T3-SV-40 cells. More interestingly, the cytotoxicity of cationized RNase As correlates well with the value of [RNase activity] x [estimated concentration of RNase free from RNase inhibitor], mimicking the practical enzymatic activity of cationized RNase As in cytosol. The results indicate that cationization of a protein to an optimum level is important for maintaining protein function in the cytosol. Sophisticated protein cationization techniques will help to advance protein transduction technology.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonuclease Pancreático
/
Sobrevivência Celular
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biochem
Ano de publicação:
2002
Tipo de documento:
Article