No abstract

SynopsisThe biologically active ACTH( 1-32) and ACTH(1-24) and other shorter peptide segments of the native hormone ACTH(1-39) were studied in aqueous solution by 13C-nmr. In order to identify the 13C resonances-except those of the carbonyls-both high-field nmr spectroscopy measurements and substitution of residues with amino acids enriched to 85% in I3C were carried out. The main results are (1) the direct characterization of the cis-trans isomerism of proline 24 and its effects on the directly connected and sequentially neighboring residues and (2) findings that the conformational features agree with an a-helix type organization in the N-terminal part of the ACTH molecule which is responsible for the biological activity.

Die Synthese der Pentafluorphenylester von Boc-Aminosauren und geschiitzten Peptiden wird beschrieben. Das Ziel der Untersuchungen war die racemisierungsfreie Herstellung der Pentafluorphenylester von Modellpeptiden und deren Kupplungsreaktionen. The Utilization of Pentafluorophenyl Esters in Peptide SynthesesThe synthesis of pentafluorophenyl esters of Boc-amino acids and protected peptides is described. The aim of the investigations was to prepare racemate-free pentafluorophenyl esters of model peptides and to study their coupling reactions.Uber die hohe Reaktivitat von Pentafluorphenylestern wurde in mehreren Arbeiten berichtet 1-3). Die Vorteile dieser hohen Reaktivitat konnten vorzuglich beim Verknupfen groBerer Peptidbruchstucke ausgenutzt werden, so z. B. bei der Synthese von menschlichem ACTH mit korrigierter Sequenz und seiner Fragmente4). Bei dieser Synthese war jedoch die C-endstandige Aminosaure der acylierenden Peptide stets Glycin oder Prolin, es bestand also keine Gefahr der Racemisierung. Wir hielten es fur wichtig, diese Methode auf die Synthese anderer Peptide auszudehnen.Fur unsere Synthesen waren Pentafluorphenylester von Boc-Aminosauren uner-1aBlich. Diese wurden mit Hilfe von DCC hergestellt. Die Daten einiger Boc-Aminosaure-pentafluorphenylester sind in Tabelle 1 angefiihrt. *) Korrespondenz bitte an diesen Autor richten.

Twenty-four thyrotropin-releasing hormone (TRH) analogues containing mainly aliphatic amino acids in position 2 were synthesized and tested for central nervous system (CNS) and hormonal (TSH) activity. Application of the pentafluorophenyl ester method in the syntheses resulted in optimal yields and high purity of the products. The neutral tripeptides pGlu- Nva -Pro-NH2 (9), pGlu-Nle-Pro-NH2 (10), and pGlu-Leu-Pro-NH2 (3) with a three- or four-membered straight or branched alkyl side chain in the position of the central amino acid had 2.5 to 10 times stronger anticataleptic effect than TRH, demonstrating that the presence of histidine is not essential for the CNS activity. Analogue 9 exhibited tenfold anticataleptic activity as compared to TRH, and it was found to be fully inactive in the release of TSH.

No abstract