Development of target protein-selective degradation inducer for protein knockdown

Bioorg Med Chem. 2011 May 15;19(10):3229-41. doi: 10.1016/j.bmc.2011.03.057. Epub 2011 Mar 29.

Abstract

Our previous technique for inducing selective degradation of target proteins with ester-type SNIPER (Specific and Nongenetic Inhibitor-of-apoptosis-proteins (IAPs)-dependent Protein ERaser) degrades both the target proteins and IAPs. Here, we designed a small-molecular amide-type SNIPER to overcome this issue. As proof of concept, we synthesized and biologically evaluated an amide-type SNIPER which induces selective degradation of cellular retinoic acid binding protein II (CRABP-II), but not IAPs. Such small-molecular, amide-type SNIPERs that induce target protein-selective degradation without affecting IAPs should be effective tools to study the biological roles of target proteins in living cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Amides / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Neuroblastoma / metabolism
  • Receptors, Retinoic Acid / metabolism*
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*

Substances

  • Amides
  • Inhibitor of Apoptosis Proteins
  • Receptors, Retinoic Acid
  • Small Molecule Libraries
  • retinoic acid binding protein II, cellular