Synthesis and metabolic stability of a tritium-labelled substance P analogue

The authors have described the synthesis of a substance P analogue, < Glu--Gln--Phe--MePhe--MeGly--Leu--Met-NH sub(2). The peptide, referred to herein as DiMe-C7, was designed to be resistant to a substance P degrading enzyme purified from brain. Evidence for the increased stability of DiMe-C7 in rat brain preparations has been presented. Moreover, DiMe-C7 exhibited a high potency in competing for tritiated substance P binding to rat brain membranes as well as retaining biological activities in peripheral substance P bioassays. This report describes the synthesis of the precursor, production of the radiolabelled peptide by catalytic dehalogenation and further evidence for enhanced resistance of DiMe-C7 to in vitro and in vivo digestion by rat brain compared with substance P.