Bifunctional epitope-agonist ligands of the bradykinin B(2) receptor

Biol Chem. 2013 Mar;394(3):379-83. doi: 10.1515/hsz-2012-0286.

Abstract

Two bradykinin (BK) B(2) receptor agonists N-terminally extended with the myc epitope were synthesized and evaluated: myc-KPG-BK and myc-KGP-B-9972. The latter was modeled on the inactivation-resistant agonist B-9972 (D-Arg(0), Hyp(3), Igl(5), Oic(7), Igl(8)-BK) and is also resistant to endosomal inactivation. Despite a large loss of affinity relative to the parent peptide, the tagged analogs are conventional agonists in the umbilical vein contractility assay and compete for [(3)H]BK binding at the rabbit B(2) receptor. Endocytosed myc-KGP-B-9972 most effectively carried AlexaFluor-488-conjugated anti-myc monoclonal antibodies into intact cells expressing the B(2) receptor. Results support the prospects of functionally-active cargoes entering cells in a pharmacologically controlled manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Drug Design
  • Endocytosis
  • Epitopes / metabolism*
  • Genes, myc
  • HEK293 Cells
  • Humans
  • Ligands*
  • Molecular Sequence Data
  • Receptor, Bradykinin B2 / agonists*

Substances

  • Epitopes
  • Ligands
  • Receptor, Bradykinin B2