• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jun 1978; 75(6): 2636–2640.
PMCID: PMC392617

Conformationally restricted bicyclic analogs of somatostatin.


A model for a biologically active conformation of somatostatin is proposed. This model is based primarily on the biological results obtained with novel bicyclic somatostatin analogs having a covalent bridge replacing the side chains of residues 5 and 10, 6 and 11, and 5 and 12, respectively, rather than on physical measurements on the hormone in solution. The high activity of an analog in which Phe6 and Phe11 are replaced by cystine provides evidence that these phenylalanines stabilize the biologically active conformer through "hydrophobic bonding" but do not directly interact with the receptor. The synthesis of the novel bicyclic analogs of somatostatin and the effects of these on the inhibition of secretion of insulin, glucagon, growth hormone, and gastric acid are described.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1005K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Holladay LA, Puett D. Somatostatin conformation: evidence for a stable intramolecular structure from circular dichroism, diffusion, and sedimentation equilibrium. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1199–1202. [PMC free article] [PubMed]
  • Holladay LA, Rivier J, Puett D. Conformational studies on somatostatin and analogues. Biochemistry. 1977 Nov 1;16(22):4895–4900. [PubMed]
  • Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science. 1973 Jan 5;179(4068):77–79. [PubMed]
  • Chandrasekaran R, Lakshminarayanan AV, Pandya UV, Ramachandran GN. Conformation of the LL and LD hairpin bends with internal hydrogen bonds in proteins and peptides. Biochim Biophys Acta. 1973 Mar 23;303(1):14–27. [PubMed]
  • KAUZMANN W. Some factors in the interpretation of protein denaturation. Adv Protein Chem. 1959;14:1–63. [PubMed]
  • Rivier JE, Brown MR, Vale WW. Tyrosylated analogues of somatostatin. J Med Chem. 1976 Aug;19(8):1010–1013. [PubMed]
  • Vale W, Brazeau P, Rivier C, Brown M, Boss B, Rivier J, Burgus R, Ling N, Guillemin R. Somatostatin. Recent Prog Horm Res. 1975;31:365–397. [PubMed]
  • Rivier J, Brown M, Vale W. D-Trp8-somatostatin: an analog of somatostatin more potent than the native molecule. Biochem Biophys Res Commun. 1975 Jul 22;65(2):746–751. [PubMed]
  • Kamber B. Cystinpeptide aus (S-Acetamidomethyl-cystein)-peptiden durch Oxydation mit Jod: Die Synthese von cyclo-L-Cystin. Helv Chim Acta. 1971;54(3):927–930. [PubMed]
  • Herbert V, Lau KS, Gottlieb CW, Bleicher SJ. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. [PubMed]
  • Torchiana ML, Stone CA, Cook PG, Weise SJ. Effect of new synthetic analogs of somatostatin on gastric secretion in the chronic fistula dog. Proc Soc Exp Biol Med. 1977 Mar;154(3):449–452. [PubMed]
  • Momany FA. Conformational energy analysis of the molecule, luteinizing hormone-releasing hormone. I. Native decapeptide. J Am Chem Soc. 1976 May 12;98(10):2990–2996. [PubMed]
  • Momany FA. Conformational energy analysis of the molecule, luteinizing hormone-releasing hormone. 2. Tetrapeptide and decapeptide analogues. J Am Chem Soc. 1976 May 12;98(10):2996–3000. [PubMed]
  • Walter R, Schwartz IL, Darnell JH, Urry DW. Relation of the conformation of oxytocin to the biology of neurohypophyseal hormones. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1355–1359. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...