Exploiting protein cationization techniques in future drug development

Junichiro Futami, Midori Kitazoe, Hitoshi Murata, Hidenori Yamada

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The development of a method for the efficient intracellular delivery of inherently non-permeable proteins is needed for manipulation of cellular phenotypes or the discovery of protein-based drugs. It has been demonstrated that proteins artificially cationized by chemical conjugation show efficient intracellular delivery via adsorptive-mediated endocytosis and then can exert their biological activity in cells. Studies have also revealed that cationic peptides known as cell-penetrating peptides (CPPs) provide a means to deliver molecules into mammalian cells. Although the internalization mechanisms remain controversial, it is now becoming clear that the main port of entry into cells by CPPs also involves adsorptive-mediated endocytosis rather than the direct penetration of the plasma membrane. As the mammalian cell membrane possesses an abundance of negatively charged glycoproteins and glycosphingolipids, cationization of proteins is a reasonable choice to endow them with the ability for intracellular delivery. Cationization of proteins is usually accompanied by drastic changes in protein properties, structure and biological activities. Recently developed sophisticated protein chemistry can minimize these side effects. Therefore, protein cationization techniques will hopefully prove to be powerful tools for innovative research and drug discovery. In this review, techniques for cationization of proteins and their intracellular delivery, as well as some of their potential therapeutic applications, are discussed.

Original languageEnglish
Pages (from-to)261-269
Number of pages9
JournalExpert Opinion on Drug Discovery
Volume2
Issue number2
DOIs
Publication statusPublished - Feb 2007

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Keywords

  • Chemical conjugation
  • In-cell folding
  • Polyethylenimine
  • Protein engineering
  • Protein transduction

ASJC Scopus subject areas

  • Drug Discovery

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