Bifunctional epitope-agonist ligands of the bradykinin B2 receptor

Abstract

Two bradykinin (BK) B2 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-Arg0, Hyp3, Igl5, Oic7, Igl8-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 [3H]BK binding at the rabbit B2 receptor. Endocytosed myc-KGP-B-9972 most effectively carried AlexaFluor-488-conjugated anti-myc monoclonal antibodies into intact cells expressing the B2 receptor. Results support the prospects of functionally-active cargoes entering cells in a pharmacologically controlled manne