Synthesis and evaluation of a UMI-77-based fluorescent probe for selective detecting Mcl-1 protein and imaging in living cancer cells

Bioorg Med Chem. 2021 Jan 1:29:115850. doi: 10.1016/j.bmc.2020.115850. Epub 2020 Nov 7.

Abstract

Development of efficient fluorescent probes for detecting the overexpressed Mcl-1 protein in living cells is imperative for the diagnosis and treatment of cancers. In this paper, a new UMI-77 based fluorescent probe (DNSH), was synthesized and characterized. DNSH bound to the hydrophobic pockets of Mcl-1 protein tightly and the binding affinity was 20-fold higher than that of previous developed Mcl-1 probe. DNSH exhibited specific fluorescence response to Mcl-1 protein rather than other proteins. In the presence of Mcl-1 protein, fluorescence emission of DNSH can be switched on. Furthermore, fluorescence colocalization experiment demonstrated that DNSH can be successfully used for imaging mitochondrial Mcl-1 protein in human prostate cancer cells without a washing process. These results showed that DNSH may find useful applications in biological research such as tracking Mcl-1 protein in living biological specimens.

Keywords: Cancer cells imaging; Fluorescent probe; Mcl-1 protein; UMI-77.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • Humans
  • Male
  • Models, Molecular
  • Molecular Structure
  • Myeloid Cell Leukemia Sequence 1 Protein / analysis*
  • Optical Imaging*
  • Prostatic Neoplasms / diagnostic imaging*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Thioglycolates / chemical synthesis
  • Thioglycolates / chemistry*

Substances

  • Fluorescent Dyes
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Sulfonamides
  • Thioglycolates
  • UMI-77