An artificially designed pore-forming protein with anti-tumor effects

J Biol Chem. 2003 Sep 12;278(37):35311-6. doi: 10.1074/jbc.M300474200. Epub 2003 May 14.

Abstract

Protein engineering is an emerging area that has expanded our understanding of protein folding and laid the groundwork for the creation of unprecedented structures with unique functions. We previously designed the first native-like pore-forming protein, small globular protein (SGP). We show here that this artificially engineered protein has membrane-disrupting properties and anti-tumor activity in several cancer animal models. We propose and validate a mechanism for the selectivity of SGP toward cell membranes in tumors. SGP is the prototype for a new class of artificial proteins designed for therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Cell Survival / drug effects*
  • Computer Simulation
  • Drug Design
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Protein Folding
  • Proteins / chemical synthesis*
  • Proteins / therapeutic use*
  • Sarcoma, Kaposi / drug therapy
  • Sarcoma, Kaposi / pathology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Proteins