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Development and Synthesis of Bombesin-Based Radiopharmaceutical Precursors Modified with Knottin.

E A Beloborodov1, E V Iurova2, A N Fomin3

  • 1Researcher, Laboratory for Peptide Drugs and Vaccines Development, S.P. Kapitsa Research Institute of Technology; Ulyanovsk State University, 42 Leo Tolstoy St., Ulyanovsk, 432017, Russia.

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|November 14, 2024
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Summary

Modified bombesin peptides show enhanced stability and binding affinity for cancer therapy. This knottin-peptide conjugate offers a promising strategy for targeted cancer treatment by improving peptide drug stability.

Keywords:
bombesinbombesin receptorknottinpeptide toxintargeted therapy

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Bombesin receptors are key targets for cancer therapy.
  • Short peptides are used for targeting but suffer from poor in vivo stability.
  • Knottin domains can enhance peptide stability.

Purpose of the Study:

  • To investigate the chemical and radiochemical stability of a bombesin peptide modified with a knottin.
  • To assess the binding ability of the modified peptide to tumor cells.

Main Methods:

  • Solid-phase peptide synthesis was used to create a fluorescent-labeled peptide.
  • High-performance liquid chromatography (HPLC) analyzed chemical and radiochemical stability of a lutetium-labeled peptide.
  • Binding assays were performed on cell cultures expressing bombesin receptors.

Main Results:

  • The knottin-modified peptide demonstrated superior chemical and radiochemical stability compared to a commercial analog.
  • The modified peptide retained high binding affinity for bombesin receptors on cancer cells.
  • The structure maintained its ability to bind to tumor cells.

Conclusions:

  • The novel bombesin peptide-knottin structure exhibits enhanced stability and retains tumor cell binding.
  • This approach provides a stabilizing scaffold for short peptides in peptide-receptor therapy.
  • The findings support the development of these structures for targeted cancer treatment.