Synthesis of Somatostatin. Preliminary communication

Immer, H.; Sestanj, K.; Nelson, V.; Götz, Manfred

doi:10.1002/hlca.19740570326

Cited by 31 publications

(5 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…the primary structure of this tetradecapeptide was established (Brazeau et al, 1973;, it was synthesized by several groups (Rivier et al, 1973;; Yamashiro and Li, 1973;Immer et al, 1974). In clinical studies this substance was shown to suppress not only the release of GH and thyrotropin from the pituitary (Hall et al, 1973;Siler et al, 1973), but also to inhibit the secretion of glucagon and insulin (Yen et al, 1974; Mortimer et al, 1974) as well as gastrin (Bloom et al, 1974).…”

mentioning

confidence: 99%

Isolation and structure of somatostatin from porcine hypothalami

Schally¹,

Dupont²,

Arimura³

et al. 1976

Biochemistry

178

View full text Add to dashboard Cite

The isolation and structure of somatostatin (GH-RIH) from pig hypothalami are described. This hormone was purified by preparative gel filtration, solvent extraction, countercurrent distribution in two solvent systems, ion-exchange and partition chromatography, and analytical gel filtration. The somatostatin activity was followed by in vitro bioassays and a radioimmunoassay. The isolated product was homogeneous chromatographically and had biological and immunological properties similar to synthetic somatostatin corresponding to the ovine hormone. The primary structure of porcine somatostatin was shown to be H-Ala-Gly-cyclo-(Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys)-OH. Other immunologically and biologically active form(s) of somatostatin were also detected.

show abstract

mentioning

confidence: 99%

Isolation and structure of somatostatin from porcine hypothalami

Schally¹,

Dupont²,

Arimura³

et al. 1976

Biochemistry

178

View full text Add to dashboard Cite

show abstract

“…The somatostatin studied in this work is the active form of 14 aminoacidic residues peptide 2,3 with an internal disulfide bridge as shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…Somatostatin is a synthetic peptide formed of 14 natural L‐aminoacidic residues, and it contains one disulfide bridge between two cysteine residues of the molecule 2,3 …”

Section: Introductionmentioning

confidence: 99%

“…1 The alternate cleavage of a single preproprotein yields two active forms of somatostatin, one with 14 amino acids and the other with 28 amino acids. 2,3 The somatostatin studied in this work study refers to the active form constituted with 14 amino acids.…”

mentioning

confidence: 99%

“…Somatostatin is a synthetic peptide formed of 14 natural Laminoacidic residues, and it contains one disulfide bridge between two cysteine residues of the molecule. 2,3 A solution containing somatostatin at 6 mg/mL was spiked with H 2 O 2 to reach the final concentration of 0.0004% and 0.004%. The reaction was performed at 25 C for 24 h. Remarkably, somatostatin showed oxidation products at trace levels.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Characterization by LC–MS/MS of oxidized products identified in synthetic peptide somatostatin and cetrorelix submitted to forced oxidative stress by hydrogen peroxide: Two case studies

Datola¹,

Pistacchio²,

Simone³

et al. 2023

J Mass Spectrom

View full text Add to dashboard Cite

In a broader scenario, the forced degradation studies provided by the ICH guidelines for Q1A, Q1B, and Q2B degradation studies allow to know the CQA of the molecule used as a drug product, to determine the appropriate analytical methods, excipients, and storage conditions ensuring the quality of the drug, its efficacy, and patient safety. In this study, we focused our attention on understanding how oxidative stress is performed by H 2 O 2 -impacted small synthetic peptides that do not contain residues susceptible to oxidation such as methionine. Among the amino acids susceptible to oxidation, methionine is the most reactive and depending on the structure of the protein where it is exposed, it tends to oxidize by converting into methionine sulfone or methionine sulfoxide by oxidation of its sulfur atom. Scouting experiments obtained by forced oxidative stress conditions are presented on two small synthetic peptides that do not contain any methionine residues spiked with different amounts of H 2 O 2 , and they are analyzed by LC-MS/MS. Less frequent oxidation products than those commonly observed on proteins/peptides-containing methionine have been characterized on both peptides. The study demonstrated that somatostatin, by means of one residue of tryptophan on the molecule, can generate traces of several oxidized products detected by UPLC-MS. Furthermore, even at a negligible level, oxidation on tyrosine and proline in cetrorelix that does not contain methionine nor tryptophan has been detected by UHPLC-MS/MS. Identification and quantification of oxidized species were achieved by high-resolution MS and MS/MS experiments. Thus, FDSs undoubtedly aid the evaluation of the CQAs as an important component of the characterization package as recommended by HAs and ICH, facilitating the understanding of unforeseen features of the studied molecule used as drugs.

show abstract

Pharmachemie im Wandel – Probleme und Chancen

König

1980

Angew. Chem.

View full text Add to dashboard Cite

Unzufrieden mit der Empirie von gestern, gedrangt von hohen Erwartungen der Offentlichkeit und unter dem Druck steigender Kosten sucht die Pharmaforschung nach neuen Wegen. Fur den Pharmachemiker folgt daraus ein Umbruch seines Arbeitsfeldes: Molekularbiologische Vorstellungen bestimmen zunehmend seine Syntheseplanung. Neue Wirkstoflklassen fordern iiber das moderne Repertoire der praparativen organischen Chemie hinaus die Ausarbeitung enzymatischer, biotechnologischer und gentechnologischer Synthesen. Durch die Entwicklung zuverlassiger Modelle der Struktur-Wirkungs-Beziehungen sucht der Pharmachemiker seine Arbeit zu rationalisieren. Der Bereich seiner Aufgaben erstreckt sich von der physikalisch-organischen Chemie iiber die Synthese bis weit hinein in die Biowissenschaften; der interdisziplinare Charakter dieser Forschung wird in Zukunft noch starker ausgepragt sein. -Dieses komplizierte Bild wird im vorliegenden Beitrag durch einige Beispiele erlautert.[*] Aus unserer Sicht sollte dieser Begriff mit groBter Vorsicht und keinesfalls polemisch gebraucht werden, denn schon Paul Ehrlich entwickelte rationale Vorstellungen iiber Rezeptoren und pharmakophore Gruppen (Schliissel-SchloB-Theorie), und seither versucht jede Generation an Pharmaforschern mit allen zu Gebote stehenden Mitteln rational vorzugehen. Die zweite Bedeutung des englischen ,,rational", namlich rationell, soilte yon der Arbeitsorganisation her uberall angestrebt werden; im Sinne quantitativer Vorhersagbarkeit von Wirkungsstarken und Wirkungsprofilen mil mathematischen Beziehungen gibt es (noch) deutliche Grenzen. Warum dies so ist, illustriert z. B. Abb. 1 durch die verschiedenartigen unter Umstanden gegenlaufigen Faktoren der Arzneimittelwirkung. 0044-824U/80/l0~0-0802 $ 02.50/0 Angew. Chem. 92, 802-815 (1980) den. Angew. Chem. 92, 8 1 5 4 3 2 (1980) 0 Verlag Chemie, CmbH, 0-6940 Weinheim, 19x0 0044-8249/8O/I010-0S15 $ 02.50/0

show abstract

Synthesis of Somatostatin. Preliminary communication

Abstract: A tetradecapeptide with the proposed structure of growth hormone release inhibiting factor was synthesized by a classical fragment approach.

Cited by 31 publications

References 9 publications

Isolation and structure of somatostatin from porcine hypothalami

Isolation and structure of somatostatin from porcine hypothalami

Characterization by LC–MS/MS of oxidized products identified in synthetic peptide somatostatin and cetrorelix submitted to forced oxidative stress by hydrogen peroxide: Two case studies

Pharmachemie im Wandel – Probleme und Chancen

Contact Info

Product

Resources

About