Carborane as an Alternative Efficient Hydrophobic Tag for Protein Degradation

Yasunobu Asawa, Kei Nishida, Kazuki Kawai, Kiyotaka Domae, Hyun Seung Ban, Akihiro Kitazaki, Hiroya Asami, Jun Ya Kohno, Satoshi Okada, Hiraku Tokuma, Daisuke Sakano, Shoen Kume, Masaru Tanaka, Hiroyuki Nakamura

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Carboranes 1 and 2 were designed and synthesized for hydrophobic tag (HyT)-induced degradation of HaloTag fusion proteins. The levels of the hemagglutinin (HA)-HaloTag2-green fluorescent protein (EGFP) stably expressed in Flp-In 293 cells were significantly reduced by HyT13, HyT55, and carboranes 1 and 2, with expression levels of 49, 79, 43, and 65%, respectively, indicating that carborane is an alternative novel hydrophobic tag (HyT) for protein degradation under an intracellular environment. To clarify the mechanism of HyT-induced proteolysis, bovine serum albumin (BSA) was chosen as an extracellular protein and modified with maleimide-conjugated m-carborane (MIC). The measurement of the ζ-potentials and the lysine residue modification with fluorescein isothiocyanate (FITC) of BSA-MIC conjugates suggested that the conjugation of carborane induced the exposure of lysine residues on BSA, resulting in the degradation via ubiquitin E3 ligase-related proteasome pathways in the cell.

Original languageEnglish
Pages (from-to)2377-2385
Number of pages9
JournalBioconjugate Chemistry
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 17 2021

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Carborane as an Alternative Efficient Hydrophobic Tag for Protein Degradation'. Together they form a unique fingerprint.

Cite this