Enhanced Serum Proteolysis Resistance of cell-penetrating Peptides

Abstract

Aim: Before starting preclinical studies, we have analyzed the integrity in serum of DPT-C9h, a promising therapeutic peptide, and performed modifications in order to improve its stability. Materials & methods: Mutant peptides exchanging arginine 8 for either lysine, asparagine or alanine were synthesized and compared with the parental peptide. Results: All mutants clearly improved peptide stability while keeping their functional activity. PK studies showed an enhanced stability, being Mut3DPT-C9h the most promising candidate. Biodistribution studies demonstrate that the modified peptide is able to reach the targeted tumor and accumulate there at higher concentration than the parental peptide. Discussion: Small modifications in the peptide sequence result in improvements allowing the selection of better candidates for preclinical studies.

Financial & competing interests disclosure

This work was supported by ANR Emergence and by Ministerio de Economía y Competitividad (SAF2012–31405), Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.