Tritiated peptides. Part 15. Synthesis of tritium labelled biologically active analogues of somatostatin

Abstract

The syntheses are described of cyclo-{[D-Trp⁸,Gaba¹²]somatostatin-(5–12)-peptide}(77), and (79)–(82) labelled singly at positions 6, 7, 8, and 11 and doubly at residues 6 and 11 to specific radioactivities of between 4.8 and 22.4 Ci mmol^–1. The linear sequence (5–12) and the related cyclo-{[D-Trp⁸,Nag¹²]somatostatin-(5–12)-peptide}(78) and (83) were also prepared to specific radioactivities of 19.2 and 19.6 Ci mmol^–1 respectively. The syntheses of the labelled hexapeptide cyclo-{[4-³H-Phe⁷,D-Trp⁸,Pro¹²] somatostatin-(7–12)-peptide}(84) and the full sequences [4-³H-Phe⁶,D- Trp⁸,D-Cys¹⁴]somatostatin (94) and [D-Trp⁸,4-³H-Phe¹¹,D-Cys¹⁴]somatostatin (95) labelled at ca. 13.0 Ci mmol^–1 are described. Labelling was effected by reductive dehalogenation in the presence of tritium of the fully protected precursors and the purity of the final products was assessed by amino acid analysis after acidic hydrolysis following purification by ion-exchange and h.p.l.c. as appropriate.