Optimum modification for the highest cytotoxicity of cationized ribonuclease

Junichiro Futami, Emiko Nukui, Takashi Maeda, Megumi Kosaka, Hiroko Tada, Masaharu Seno, Hidenori Yamada

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)223-228
Number of pages6
JournalJournal of Biochemistry
Volume132
Issue number2
Publication statusPublished - Aug 2002

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Cytotoxicity
Ribonucleases
Proteins
Pancreatic Ribonuclease
ethylenediamine
Cytosol
Coulomb interactions
Static Electricity
Technology
Neoplasms

Keywords

  • Cationization
  • Cytotoxicity
  • Protein transduction
  • Ribonuclease

ASJC Scopus subject areas

  • Biochemistry

Cite this

Optimum modification for the highest cytotoxicity of cationized ribonuclease. / Futami, Junichiro; Nukui, Emiko; Maeda, Takashi; Kosaka, Megumi; Tada, Hiroko; Seno, Masaharu; Yamada, Hidenori.

In: Journal of Biochemistry, Vol. 132, No. 2, 08.2002, p. 223-228.

Research output: Contribution to journalArticle

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AU - Seno, Masaharu

AU - Yamada, Hidenori

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