title: Enhanced serum proteolysis resistance of cell-penetrating peptides.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Small modifications in the peptide sequence result in improvements allowing the selection of better candidates for preclinical studies.
authors.affiliation: CIMI-Paris, UPMC UMRS CR7-Inserm U1135-CNRS ERL 8255, Faculte de Medicine Pierre et Marie Curie, CHU Pitié Salpêtrière, 91, Bd de 1-Hôpital, 75013 Paris, France.
authors.forename: Jesús
authors.initials: J
authors.lastname: Fominaya
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Bravo
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin
authors.forename: Jean Yves
authors.initials: JY
authors.lastname: Brossa
authors.forename: Fariba
authors.initials: F
authors.lastname: Nemati
authors.forename: Angelita
authors.initials: A
authors.lastname: Rebollo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D008819:Mice, Nude; D009154:Mutation; D059748:Proteolysis; D020539:Sequence Analysis, Protein; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D057846:Cell-Penetrating Peptides; C000597418:DPT-C9h peptide