Cellular uptake of an α-AApeptide

Org Biomol Chem. 2012 Feb 14;10(6):1149-53. doi: 10.1039/c2ob06679c. Epub 2011 Dec 23.

Abstract

Some short and cationic peptides such as the Tat peptide can cross the cell membrane and function as vectors for intracellular delivery. Here we show that an α-AApeptide is able to penetrate the membranes of living cells from an extracellular environment and enter the endosome and cytoplasm of cells. The efficiency of the cellular uptake is comparable to a Tat peptide (48-57) of the same length and is unexpectedly superior to an α-peptide with identical functional groups. The mechanism of uptake is similar to that of the Tat peptide and is through endocytosis by an energy-dependent pathway. Due to the easy synthesis of the α-AApeptides, their resistance to proteolytic hydrolysis, and their low cytotoxicity, α-AApeptides represent a new class of transporters for the delivery of drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Cytoplasm / metabolism
  • Dose-Response Relationship, Drug
  • Endosomes / metabolism
  • Gene Products, tat / chemistry
  • Gene Products, tat / metabolism
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Molecular Conformation
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Peptides / pharmacology
  • Permeability* / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Gene Products, tat
  • Peptides