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

Die Titelverbindung ([Pap′3 1a‐ MSH) ‐ in der acetylierten Form (IIIc) ‐ wird in homogener Lösung nach klassischer r Fragmentkondensationsmethode synthetisiert [(1) + (II) ‐+ (IIIa)‐(IIIb)‐(IIIc)] und hinsichtlich ihrer biologischen Eigenschaften (Pigmentverteilungs‐Aktivität, Tyrosinase‐stimulierende Aktivität) vergleichend mit α‐Melanotropin detailliert untersucht.

Für biologische Untersuchungszwecke (Herstellung von kovalenten Hormon‐Protein‐ Komplexen und (Photo)‐Affinitätsmarkierung von Rezeptoren) werden die benötigten tritiierten α‐Melanotropin‐Analogen (IIId) und (X) sowie die α‐Melanotropin‐ Fragmente (VIIa) (9‐13), (VIIb) (5‐10) und (VIIc) (5 ‐13) synthetisiert: 1. (IIId) wird aus dem Kondensationsprodukt (IIIa) der Komponenten (I) und (II) über die 152 Stufen (IIIb) und (IIIc) gewonnen.