ChemInform Abstract: α‐MELANOTROPIN LABELED AT ITS TYROSINE2 RESIDUE: SYNTHESIS AND BIOLOGICAL ACTIVITIES OF 3′‐IODOTYROSINE2‐,3′‐125IODOTYROSINE2‐,3′,5′‐DIIODOTYROSINE2‐, AND (3′,5′‐3H2)TYROSINE2‐α‐MELANOTROPIN, AND OF RELATED PEPTIDES

Abstract

Summarya-MSH was labelled at its tyrosine' residue with tritium and iodine. Several synthetic routes were investigated by preparing 13 precursor or model compounds and 4 different labelled products (via about 40 intermediates). Their melanotropic activity was determined with an in vitro frog skin assay and, for some of the compounds, with a tyrosinase assay. The tritiation was performed on [Tyr (IJ2]u-MSH by catalytic halogedtritium exchange, yielding a-MSH of high specific radioactivity (34 Ci/mmol) and full biological activity. Iodination was studied in detail using five different techniques. An equimolar chloramine T procedure proved to be the most convenient and reproducible method, resulting in monoiodinated u-MSH containing 99% of the label in position 2. The biological activity was 50% that of a-MSH; the specific radioactivity, determined in a competitive binding assay with a highly specific a-MSH antiserum and [Tyr(I)']a-MSH as competitor, was 1530 Ci/mmol. The labelling techniques and the biological results are discussed.Introduction. -Recent findings of a possibly decisive involvement of a-melanotropin (a-MSH) in neural functioning and foetal development are the reason for renewed intense investigation of this tridecapeptide [3]. From synthetic studies on structure/function relations it appeared that different target cell receptors may recognize different portions of the a-MSH molecule [4]. In order to study such hormone-receptor interactions in more detail, a-MSH derivatives are synthesized which

Peptide-targeted radionuclide therapy for melanoma

“…Peptides that target the MC1-R and melanin were labeled with beta-particle-emitting radionuclides 188 Re [27][28][29][30][31][32], 90 Y [33], 177 Lu [33,34], 64 Cu [35][36][37], alphaparticle-emitters 212 Pb/ 212 Bi [38] and Auger-emitter 125 I [ [39][40][41][42][43]. While the therapeutic properties of 111 In-labeled somatostatin peptides have been examined in preclinical [44,45] and clinical [46,47] studies, it is likely that nuclear localization and trapping may be necessary for optimal effectiveness in cancer treatment [48].…”