A novel delivery platform for therapeutic peptides

Biochem Biophys Res Commun. 2014 Jul 18;450(1):13-8. doi: 10.1016/j.bbrc.2014.05.049. Epub 2014 May 21.

Abstract

Although many peptides have therapeutic effects against diverse disease, their short half-lives in vivo hurdle their application as drug candidates. To extend the short elimination half-lives of therapeutic peptides, we developed a novel delivery platform for therapeutic peptides using an anti-hapten antibody and its corresponding hapten. We selected cotinine because it is non-toxic, has a well-studied metabolism, and is physiologically absent. We conjugated WKYMVm-NH2, an anti-sepsis therapeutic peptide, to cotinine and showed that the conjugated peptide in complex with an anti-cotinine antibody has a significantly improved in vivo half-life while retaining its therapeutic efficacy. We suggest that this novel delivery platform for therapeutic peptides will be very useful to develop effective peptide therapeutics.

Keywords: Delivery; Peptide; Sepsis; Stability; Therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cotinine / administration & dosage*
  • Cotinine / chemistry
  • Cotinine / pharmacokinetics*
  • Drug Compounding / methods
  • Drug Delivery Systems / methods
  • Humans
  • Mice
  • Neutrophil Activation / drug effects*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Oligopeptides / administration & dosage*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacokinetics*
  • Protein Binding
  • Sepsis / diagnosis*
  • Sepsis / drug therapy*
  • Treatment Outcome

Substances

  • Oligopeptides
  • Trp-Lys-Tyr-Met-Val-Met
  • Cotinine