Knottins As A Structural Basis For The Stabilization Of Radio Pharmaceuticals

Abstract

The aim of the current reseach was to study synthesize a peptide tropic to the prostate-specific antigen and containing a cysteine knot.

 Materials and Methods: A comparative study of the efficiency of binding in vitro with prostate cancer cells of artificial peptides based on U5-scytotoxin-Sth1a toxin with an inserted peptide tropic to the prostate-specific membrane antigen and the radiopharmaceutical 177Lu-PSMA-617 is carried out. Three prostate cancer cell lines were used in the research.

 Results: Synthesized DOTA-Knot/C0-C1, DOTA-Knot/C1-C2 and DOTA-Knot/C2-C3 peptides containing the GTIQPYPFSWGY sequence inserted into U5-Sth1a knottin are more stable in blood plasma and saline and also show a similar degree of binding to LNCaP, PC3 cells compared with the 177Lu-PSMA-617 radiopharmaceutical.

Conclusion: Modified peptides with a peptide tropic to the PSMA antigen inserted into the structure of U5-Sth1a toxin demonstrate the greatest stability.