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Hormon‐Rezeptor‐Wechselwirkungen. Synthese von α‐Melanotropin und von informationstragenden Teilsequenzen unter Verwendung alkalilabiler Schutzgruppen
Author(s) -
Eberle Alex,
Fauchère JeanLuc,
Tesser Godefridus Ignatius,
Schwyzer Robert
Publication year - 1975
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19750580724
Subject(s) - chemistry , carbodiimide , benzotriazole , amino acid , peptide , stereochemistry , alkoxy group , protecting group , carboxylic acid , medicinal chemistry , organic chemistry , biochemistry , alkyl
Hormone‐Receptor Interactions. Synthesses of α‐Melanotropin and of Informational Sequences thereof with the Aid of Alcali‐Labile Protecting Groups. The aim of this investigation was to prepare α‐melanotropin and partial sequences thereof for biological investigations in as pure a state as possible. Classical synthesis in solution was chosen as the general approach, because it allows for extensive purification and identification of all intermediates, thus warranting the chemical identity of the products (in contrast to the solidphase methods). The scheme of protection was as follows: for the N α ‐amino groups mostly t‐butoxycarbonyl (BOC‐), sometimes benzyloxycarbonyl (Z‐), for the N ϵ ‐amino group of lysine‐(11) 2‐(methylsulfonyl)‐ethoxycarbonyl (MSOC‐), and for the carboxylic acid group of C‐terminal glycine‐(10) 2‐(4‐tolyl‐sulfonyl)‐ethoxy (‐OTSE). This provides for facile and mild selective deprotection of either the α‐amino groups by acidolysis or of the ϵ‐amino group (α‐carboxyl group) by β‐elimination in alcali. A slight molar excess of 0.12N HCl in HCOOH proved to be the method of choice for removing BOC‐; MSOC‐ is stable in acid (even for 30 min in liquid HF) and easily removed in a few minutes by 0.05‐‐0.1N Ba(OH) 2 ; ‐OTSE is removed similarly. Condensation of amino‐acid and peptide derivatives (formation of the peptide link) was performed using active esters (‐ONP; ‐OSU), dicyclohexyl‐carbodiimide (DCCI) with or without 1‐hydroxy‐benzotriazole (HOBT), or carboxylic acid azides wherever histidine was the carboxylic component. More than 50 compounds are described. Those characterized by arabic numerals served to prove that α‐MSH contains two message sequences that are able to trigger melanocyte response: one in the central region ‐His‐Phe‐Arg‐Trp‐, the other in the C‐terminal portion ‐Gly‐Lys‐Pro‐Val · NH 2 of the molecule [3].