Synthese von radioaktiv markierten Bromacetyl‐ und Diazoacetyl‐α‐melanotropin‐Derivaten zum Studium von kovalenten Hormon‐Makromolekül‐Komplexen

Synthesis of radioactive α‐melanotropin derivatives containing a bromoacetyl or diazoacetyl group for studies of covalent hormone‐macromolecule complexes α‐Melanotropin derivatives and fragments covalently bound to human serum albumin through their N ‐terminal end exhibit almost the same biological activity as the corresponding free N α ‐acetylated peptides [6]. The preparation of such complexes requires derivatives with a ‘reactive’ N ‐terminal acetyl group. We describe here the synthesis of three α‐melanotropin fragments and of two specifically tritiated α‐melanotropin derivatives containing N α ‐bromoacetyl or N α ‐diazoacetyl groups: BrCH 2 CO · Glu‐His‐Phe‐Arg‐Trp‐Gly‐Lys‐Pro‐Val · NH 2 , BrCH 2 CO · Glu‐His‐Phe‐Arg‐Trp‐Gly · OH, BrCH 2 CO · Trp‐Gly‐Lys‐Pro‐Val middot; NH 2 , BrCH 2 CO · D ‐Ala‐Tyr( 3 H 2 )‐Gly‐Nva‐Glu‐His‐Phe‐Arg‐Trp‐Gly‐Lys‐Pro‐Val · NH 2 , and N 2 = CHCO · Gly‐Tyr( 3 H 2 )‐Ser‐Nva‐Glu‐His‐Phe‐Arg‐Trp‐Gly‐ Lys‐Pro‐Val · NH 2 . The latter two analogues displayed a specific radioactivity of about 20 and 36 Ci/mmol, and a biological activity of 2 · 10 9 and 6 · 10 9 U/mmol respectively. They are also being used for affinity and photoaffinity labelling of receptor molecules and antibody combining sites.