Journal ArticleDOI
Hormon-Rezeptor-Wechselwirkungen. Synthese von α-Melanotropin und von informationstragenden Teilsequenzen unter Verwendung alkalilabiler Schutzgruppen
TLDR
In this article, the authors used the Alcali-labile protecting groups to protect α-melanotropin and partial sequences for biological investigations in as pure a state as possible.Abstract:
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 Nα-amino groups mostly t-butoxycarbonyl (BOC-), sometimes benzyloxycarbonyl (Z-), for the Nϵ-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 · NH2 of the molecule [3].read more
Citations
More filters
Journal ArticleDOI
Leaving groups and nucleofugality in elimination and other organic reactions
Journal ArticleDOI
α-melanotropin: The minimal active sequence in the lizard skin bioassay
Ana Maria de Lauro Castrucci,M. E. Hadley,Tomi K. Sawyer,Brian C. Wilkes,Fahad Al-Obeidi,D J Staples,A.E. de Vaux,O. Dym,M.F. Hintz,J.P. Riehm,K.R. Rao,Victor J. Hruby +11 more
TL;DR: The minimal message sequence for equipotency to alpha-MSH appears to be Ac-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-NH2, since the analog, Ac-[Nle4]-alpha- MSH4-11- NH2, was as active as the native hormone.
Journal ArticleDOI
Mechanism of action of thrombin on fibrinogen
Journal ArticleDOI
Biological and conformational studies of [Val4]morphiceptin and [D-Val4]morphiceptin analogs incorporating cis-2-aminocyclopentane carboxylic acid as a peptidomimetic for proline.
TL;DR: A comparison of the findings from the conformational analysis and biological assays establishes the fact that a relatively large separation of the two aromatic side chains is required for the mu-opioid receptor activity of these molecules.
References
More filters
Journal ArticleDOI
Eine neue Methode zur Synthese von Peptiden: Aktivierung der Carboxylgruppe mit Dicyclohexylcarbodiimid unter Zusatz von 1‐Hydroxy‐benzotriazolen
Wolfgang König,Rolf Geiger +1 more
TL;DR: In this article, the authors show that 1-Hydroxy-benzotriazol and 1-hydroxy-acetyl carbodiimid-methode eignen sich als Zusatze bei der Dicyclohexylcarbodiimids-Methode zur Synthese von Peptiden, verhindern die N-Acyl-harnstoffbildung and fuhren in hoher Ausbeute.
Journal ArticleDOI
Synthese von Zwischenprodukten für den Aufbau corticotrop wirksamer Polypeptide III. Das Decapeptid H·Ser‐Tyr‐Ser‐Met‐Glu‐His‐Phe‐Arg‐Try‐Gly·OH und einige seiner Derivate
Robert Schwyzer,H. Kappeler +1 more
TL;DR: In this paper, the synthesis of the decapeptide H·Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Try-Gly·OHt is described in detail.
Journal ArticleDOI
95. Zwei Synthesen des α-Melanotropins (α-MSH) mit Hilfe leicht entfernbarer Schutzgruppen)
Robert Schwyzer,Robert Schwyzer,Antigone Costopanagiotis,Antigone Costopanagiotis,P. Sieber,P. Sieber +5 more
Journal ArticleDOI
Hormone‐Receptor Interactions. Demonstration of Two Message Sequences (Active Sites) in α‐Melanotropin
Alex Eberle,Robert Schwyzer +1 more
TL;DR: The purpose of this investigation was to elucidate the biological significance of the tripeptide sequence 11–13, -Lys-Pro-Val · NH2 contained in α-melanocyte-stimulating hormone, and conclude that the two receptors (adrenal and melanocyte), albeit recognizing -Met-Glu-His-Phe-Arg-Trp-Gly- as stimulus, differ fundamentally in their response to -L Lys- pro-Val.
Related Papers (5)
Hormone‐Receptor Interactions. Demonstration of Two Message Sequences (Active Sites) in α‐Melanotropin
Alex Eberle,Robert Schwyzer +1 more