Identification of peptidomimetic telomere dysfunction inhibitor (TELODIN) through telomere dysfunction-induced foci

Lihui Wang1, Zhiguo Wang1, Jun-Ping Liu1,2,3,4

  • 1Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang Province 311121, China.

STAR Protocols
|July 1, 2021
PubMed

Insights

Synthetic peptides targeting FBW7, a tumor suppressor, were screened using the telomere dysfunction-induced focus (TIF) assay. This identified a peptidomimetic inhibitor that prevents radiation-induced telomere dysfunction, offering potential for aging-related disease therapies.

Area of Science:

  • Cellular biology
  • Molecular genetics
  • Biochemistry

Background:

  • Telomere dysfunction is implicated in aging and age-related diseases.
  • The telomere dysfunction-induced focus (TIF) assay is a method for detecting telomere damage.
  • FBW7 is a tumor suppressor gene product involved in protein degradation.

Purpose of the Study:

  • To screen synthetic peptides derived from FBW7 for their ability to prevent telomere dysfunction.
  • To evaluate the potential of identified inhibitors as therapeutic agents for aging-related diseases.

Main Methods:

  • Utilized the telomere dysfunction-induced focus (TIF) assay to screen synthetic peptides.
  • Exposed cells to environmental radiation stress to induce telomere dysfunction.
  • Assessed the efficacy of FBW7-derived peptides in preventing TIFs.

Main Results:

  • Identified specific synthetic peptides from FBW7 that inhibit radiation-induced TIFs.
  • Demonstrated that a peptidomimetic inhibitor can prevent telomere dysfunction.
  • Validated the utility of the TIF assay in discovering telomere dysfunction inhibitors.

Conclusions:

  • FBW7-derived peptides show promise in preventing telomere dysfunction.
  • Peptidomimetic telomere dysfunction inhibitors represent potential therapeutic candidates for aging-related diseases.
  • The TIF assay is a valuable tool for identifying novel telomere dysfunction inhibitors.