Abstract
We designed and synthesized hybrid molecules for a protein knockdown method based on the recognition of a His-tag fused to a protein of interest (POI). The synthesized target protein degradation inducers contained three functional moieties: a His-tag ligand (nickel nitrilotriacetic acid [Ni-NTA]), an E3 ligand (bestatin [BS] or MV1), and a carrier peptide (Tat or nonaarginine [R9]). The designed hybrid molecules, BS-Tat-Ni-NTA, MV1-Tat-Ni-NTA, BS-R9-Ni-NTA, and MV1-R9-Ni-NTA, efficiently degraded His-tagged cellular retinoic acid binding protein 2 via the ubiquitin-proteasome system (UPS). This system will become a useful tool for research into selective protein degradation inducers that act via the UPS.
Keywords:
Carrier peptide; His-tag-fused protein; Protein knockdown; Ubiquitin-proteasome system.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cell Line
-
Cell-Penetrating Peptides / chemistry
-
Cell-Penetrating Peptides / pharmacology*
-
Dose-Response Relationship, Drug
-
Histidine / metabolism
-
Humans
-
Leucine / analogs & derivatives*
-
Leucine / chemistry
-
Leucine / pharmacology
-
Ligands
-
Molecular Structure
-
Nitrilotriacetic Acid / analogs & derivatives*
-
Nitrilotriacetic Acid / chemistry
-
Nitrilotriacetic Acid / pharmacology
-
Oligopeptides / chemistry
-
Oligopeptides / pharmacology*
-
Organometallic Compounds / chemistry
-
Organometallic Compounds / pharmacology*
-
Receptors, Retinoic Acid / antagonists & inhibitors*
-
Receptors, Retinoic Acid / metabolism
-
Structure-Activity Relationship
-
Ubiquitin-Protein Ligases / antagonists & inhibitors*
-
Ubiquitin-Protein Ligases / metabolism
Substances
-
Cell-Penetrating Peptides
-
Ligands
-
Oligopeptides
-
Organometallic Compounds
-
Receptors, Retinoic Acid
-
nonaarginine
-
retinoic acid binding protein II, cellular
-
nickel nitrilotriacetic acid
-
Histidine
-
Ubiquitin-Protein Ligases
-
Leucine
-
ubenimex
-
Nitrilotriacetic Acid