Modulation of BACE1 Activity by Chemically Modified Aptamers

Chembiochem. 2018 Apr 4;19(7):754-763. doi: 10.1002/cbic.201700461. Epub 2018 Feb 19.

Abstract

A modified DNA aptamer that binds BACE1, a therapeutic target involved in Alzheimer's disease has been developed. This ssXNA not only tightly binds to BACE1 but also inhibits its protease activity in vitro in the same range as a previously described unmodified aptamer. We report the in vitro selection of functional oligonucleotides incorporating two nucleobase modifications: 5-chlorouracil and 7-deazaadenine. The nucleoside analogue 5-chloro-2'-deoxyuridine has already been explored as a replacement for thymidine in a chemically modified genome of a bacterium. Thus, 5-chlorouracil modification is a good candidate to support genetic transfer in vivo as well as functional activity.

Keywords: BACE1; XNA; aptamers; inhibitors; secretases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / chemistry
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / metabolism*
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / metabolism*
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / metabolism*
  • Base Sequence
  • Humans
  • Protein Binding
  • SELEX Aptamer Technique
  • Uracil / analogs & derivatives
  • Uracil / chemistry

Substances

  • Aptamers, Nucleotide
  • 7-deazaadenine
  • Uracil
  • 5-chlorouracil
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • Adenine