Skip to main content
SpringerLink
Log in

Guiding principles applied in the design of GPCR-selective hypothalamic hormone agonists and antagonists

  • Conference paper
Insights into Receptor Function and New Drug Development Targets

Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI))

  • 502 Accesses

Summary

Strategies for the design of peptide agonists and antagonists of gonadotropin releasing hormone (GnRH, one ligand and one receptor) and of receptor-selective agonists and antagonists of somatostatin (SRIF, three ligands and five receptors) and corticotropin releasing factor (CRF, three ligands and two receptors) are described. These strategies include the use of unusual amino acids, a versatile scaffold based on aminoglycine (betidamino acids) and side chain as well as backbone conformational constraints.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adams BA, Tello J, Erchegyi J, Warby C, Hong DJ, Akinsanya KO, Mackie GO, Vale W, Rivier JE, Sherwood NM (2003) Six novel GnRH hormones are encoded as triplets on each of two genes in protochordate Ciona intestinalis. Endocrinology 144:1907–1919

    Article  PubMed  CAS  Google Scholar 

  • Bauer W, Briner U, Doepfner W, Haller R, Huguenin R, Marbach P, Petcher TJ, Pless J (1982) SMS 201–995: a very potent and selective octapeptide analog of somatostatin with prolonged action. Life Sci 31:1133–1140

    Article  PubMed  CAS  Google Scholar 

  • Boler J, Enzmann F, Folkers K, Bowers CY, Schally AV (1969) The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyro-glutamyl-histidyl-proline amide. Biochem Biophys Res Commun 37:705–710

    Article  PubMed  CAS  Google Scholar 

  • Brazeau P, Vale WW, Burgus R, Ling N, Butcher M, Rivier JE, Guillemin R (1973) Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179:77–79

    PubMed  CAS  Google Scholar 

  • Broadbear JH, Winger G, Rivier J, Rice KC, Woods JH (2004) Corticotropin-releasing-hormone antagonists, Astressin B and Antalarmin: Differing profiles of activity in Rhesus Monkeys. Neuropsychopharmacology 29:1112–1121

    Article  PubMed  CAS  Google Scholar 

  • Broqua P, Riviere P, Conn PM, Rivier JE, Aubert MK, Junien J-L (2002) Pharmacological profile of a new, potent and long-acting gonadotropin-releasing hormone antagonist: Degarelix. J Pharmacol Exper Ther 301:95–102

    Article  CAS  Google Scholar 

  • Bruno JF, Xu Y, Song J, Berelowitz M (1992) Molecular cloning and functional expression of a brain-specific somatostatin receptor. Proc Natl Acad Sci USA 89:11151–11155

    Article  PubMed  CAS  Google Scholar 

  • Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G (2002) SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146:707–716

    Article  PubMed  CAS  Google Scholar 

  • Burgus R, Dunn T, Desiderio D, Ward D, Vale WW, Guillemin R (1970) Characterization of the ovine hypothalamic hypophysiotropic TSH-releasing factor (TRF). Nature 226:321–325 (25) Guillemin R, Brazeau P, Bohlen P, Esch F, Ling N, Wehrenberg WB (1982) Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science 218:585–587

    Article  PubMed  CAS  Google Scholar 

  • Burgus R, Butcher M, Amoss M, Ling N, Monahan M, Rivier J, Fellows R, Blackwell R, Vale WW, Guillemin R (1972) Primary structure of the ovine hypothalamic luteinizing hormone-releasing factor (LRF). Proc Natl Acad Sci USA 69:278–282

    Article  PubMed  CAS  Google Scholar 

  • Carolsfeld J, Powell JFF, Park M, Fisher WH, Craig AG, Chang JP, Rivier JE, Sherwood NM (2000) Primary structure and function of three gonadotropin-releasing hormones, including a novel form, from an ancient teleost, herring. Endocrinology 141:505–512

    Article  PubMed  CAS  Google Scholar 

  • Cho N, Harada M, Imaeda T, Imada T, Matsumoto H, Hayase Y, Sasaki S, Furuya S, Suzuki N, Okubo S, Ogi K, Endo S, Onda H, Fujino M (1998) Discovery of a novel, potent, and orally active nonpeptide antagonist of the human luteinizing hormone-releasing hormone (LHRH) receptor. J Med Chem 41:4190–4195

    Article  PubMed  CAS  Google Scholar 

  • Conlon JM, Collin F, Chiang Y-C, Sower SA, Baudry H (1993) Two molecular forms of gonadotropin-releasing hormone from the brain of the frog, Rana ridibunda: purification, characterization, and distribution. Endocrinology 132:2117–2123

    Article  PubMed  CAS  Google Scholar 

  • Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW (1996a) Cloning and characterization of human urocortin. Endocrinology 137:2167–2170

    Article  PubMed  CAS  Google Scholar 

  • Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW (1996b) Cloning and characterizationof humanurocortin, erratum. Endocrinology 137:3896

    Article  PubMed  CAS  Google Scholar 

  • Erchegyi J, Waser B, Schaer J-C, Cescato R, Brazeau JF, Rivier J, Reubi JC (2003a) Novel sst4-selective somatostatin (SRIF) agonists. Part III: Analogues amenable to radiolabeling. J Med Chem 46:5597–5605

    Article  PubMed  CAS  Google Scholar 

  • Erchegyi J, Penke B, Simon L, Michaelson S, Wenger S, Waser B, Cescato R, Schaer J-C, Reubi JC, Rivier J (2003b) Novel sst4-selective somatostatin (SRIF) agonists. Part II: Analogues with β-methyl-3-(2-naphthyl)-alanine substitutions at position 8. J Med Chem 46:5587–5596

    Article  PubMed  CAS  Google Scholar 

  • Erchegyi J, Hoeger CA, Low W, Hoyer D, Waser B, Eltschinger V, Schaer J-C, Cescato R, Reubi JC, Rivier JE (2005) Somatostatin receptor 1 selective analogues: 2. N-methylated scan. J Med Chem 48:507–514

    Article  PubMed  CAS  Google Scholar 

  • Fischer W, Spiess J (1987) Identification of a mammalian glutaminyl cyclase converting glutaminyl into pyroglutamyl peptides. Proc Natl Acad Sci USA 84:3628–3632

    Article  PubMed  CAS  Google Scholar 

  • Fisher LA, Rivier C, Rivier J, Brown MR (1991) Differential antagonist activity of α-helical CRF(9-41) in three bioassay systems. Endocrinology 129:1312–1316

    PubMed  CAS  Google Scholar 

  • Fujino M, Kobayashi S, Obayashi M, Sinagawa S, Fukuda T, Kitada C, Nakayama R, Yamazaki I, White WF, Rippel RH (1972) Structure-activity relationships in the C-terminal part of luteinizing hormone releasing hormone (LH-RH). Biochem Biophys Res Commun 49:863–869

    Article  PubMed  CAS  Google Scholar 

  • Grace CRR, Erchegyi J, Koerber SC, Reubi JC, Rivier J, Riek R (2003) Novel sst4-selective somatostatin (SRIF) agonists. Part IV: Three-dimensional consensus structure by NMR. J Med Chem 46:5606–5618

    Article  PubMed  CAS  Google Scholar 

  • Grace CRR, Durrer L, Koerber SC, Erchegyi J, Reubi JC, Rivier JE, Riek R (2005) Somatostatin receptor 1 selective analogues: 4. Three-dimensional consensus structure by NMR. J Med Chem 48:523–533

    Article  PubMed  CAS  Google Scholar 

  • Guillemin R, Brazeau P, Bohlen P, Esch F, Ling N, Wehrenberg WB (1982) Growth hormonereleasing factor from a human pancreatic tumor that caused acromegaly. Science 218:585–587

    PubMed  CAS  Google Scholar 

  • Guillemin R, Vargo T, Rossier J, Minick S, Ling N, Rivier C, Vale WW, Bloom F (1977) β-Endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland. Science 197:1367–1369

    PubMed  CAS  Google Scholar 

  • Gulyas J, Rivier C, Perrin M, Koerber SC, Sutton S, Corrigan A, Lahrichi SL, Craig AG, Vale WW, Rivier J (1995) Potent, structurally constrained agonists and competitive antagonists of corticotropin releasing factor (CRF). Proc Natl Acad Sci USA 92:10575–10579

    Article  PubMed  CAS  Google Scholar 

  • Hsu SY, Hsueh AJ (2001) Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. Nat Med 7:605–611

    Article  PubMed  CAS  Google Scholar 

  • Jiang G, Stalewski J, Galyean R, Dykert J, Schteingart C, Broqua P, Aebi A, Aubert ML, Semple G, Robson P, Akinsanya K, Haigh R, Riviere P, Trojnar J, Junien JL, Rivier JE (2001) GnRH antagonists: A new generation of long acting analogues incorporating urea functions at positions 5 and 6. J Med Chem 44:453–467

    Article  PubMed  CAS  Google Scholar 

  • Jimenez-Liñan M, Rubin BS, King JC (1997) Examination of guinea pig luteinizing hormone-releasing hormone gene reveals a unique decapeptide and existence of two transcripts in the brain. Endocrinology 138:4123–4130

    Article  PubMed  Google Scholar 

  • Koerber SC, Rizo J, Struthers RS, Rivier JE (2000) Consensus bioactive conformation of cyclic GnRH antagonists defined by NMR and molecular modeling. J Med Chem 43:819–828

    Article  PubMed  CAS  Google Scholar 

  • Kornreich WD, Galyean R, Hernandez J-F, Craig AG, Donaldson CJ, Yamamoto G, Rivier C, Vale WW, Rivier JE (1992) Alanine series of ovine corticotropin releasing factor (oCRF): a structure-activity relationship study. J Med Chem 35:1870–1876

    Article  PubMed  CAS  Google Scholar 

  • Kupryszewski G, Rivier CL, Perrin M, Vale WW, Rivier J (1987) Synthesis of a new cyclic gonadotropin releasing hormone (GnRH) antagonist. Polish J Chem 61:627–630

    CAS  Google Scholar 

  • Lederis K, Letter A, McMaster D, Moore G (1982) Complete amino acid sequence of urotensin I, a hypotensive and corticotropin-releasing neuropeptide from Catostomus. Science 218:162–164

    PubMed  CAS  Google Scholar 

  • Lederis K, McMaster D, Ichikawa T, MacCannell KL, Rivier J, Rivier C, Vale W, Fryer J, Kobayashi Y (1983) Isolation, analysis of structure, synthesis, and biological actions of urotensin I neuropeptides. Can J Biochem 61:602–614

    Article  CAS  Google Scholar 

  • Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes TM, Gulyas J, Fischer W, Bilezikjian L, Rivier J, Sawchenko PE, Vale WW (2001) Identification of Urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc Natl Acad Sci USA 98:7570–7575

    Article  PubMed  CAS  Google Scholar 

  • Lewis I, Bauer W, Albert R, Chandramouli N, Pless J, Weckbecker G, Bruns C (2003) A novel somatostatin mimic with broad somatotropin release inhibitory factor receptor binding and superior therapeutic potential. J Med Chem 46:2334–2344

    Article  PubMed  CAS  Google Scholar 

  • Lovejoy DA, Fischer WH, Ngamvongchon S, Craig AG, Nahorniak CS, Peter RE, Rivier JE, Sherwood NM (1992) Distinct sequence of gonadotropin-releasing hormone (GnRH) in dogfish brain provides insight into GnRH evolution. Proc Natl Acad Sci USA 89:6373–6377

    Article  PubMed  CAS  Google Scholar 

  • Matsuo H, Baba Y, Nair RM, Arimura A, Schally AV (1971) Structure of the porcine LH-and FSH-releasing hormone. I. The proposed amino acid sequence. Biochem Biophys Res Commun 43:1334–1339

    Article  PubMed  CAS  Google Scholar 

  • Melacini G, Zhu Q, Osapay G, Goodman M (1997) A refined model for the somatostatin pharmacophore: Conformational analysis of lanthionine-sandostatin analogs. JMed Chem 40:2252–2258

    Article  CAS  Google Scholar 

  • Meyerhof W, Paust HJ, Schoenrock C, Richter D (1991) Cloning of a cDNA encoding a novel putative G-protein-coupled receptor expressed in specific rat brain regions. DNA Cell Biol 10:689–694

    Article  PubMed  CAS  Google Scholar 

  • Millar RP, Lu ZL, Pawson AJ, Flanagan CA, Morgan K, Maudsley SR (2004) Gonadotropin-releasing hormone receptors. Endocr Rev 25:235–275

    Article  PubMed  CAS  Google Scholar 

  • Miranda A, Lahrichi SL, Gulyas J, Koerber SC, Craig AG, Corrigan A, Rivier C, Vale WW, Rivier JE (1997) Constrained corticotropin releasing factor (CRF) antagonists with i-(i+3) Glu-Lys bridges. J Med Chem 40:3651–3658

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto K, Hasegawa Y, Igarashi M, Chino N, Sakakibara S, Kangawa K, Matsuo H (1983) Evidence that chicken hypothalamic luteinizing hormone-releasing hormone is [Gln8]-LHRH. Life Sci 32:1341–1347

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto K, Hasegawa Y, Nomura M, Igarashi M, Kangawa K, Matsuo H (1984) Identification of the second gonadotropin-releasing hormone in chicken hypothalamus: evidence that gonadotropin secretion is probably controlled by two distinct gonadotropin-releasing hormones in avian species. Proc Natl Acad Sci USA 81:3874–3878

    Article  PubMed  CAS  Google Scholar 

  • Monahan M, Amoss M, Anderson H, Vale W (1973) Synthetic analogs of the hypothalamic luteinizing hormone releasing factor with increased agonist or antagonist properties. Biochem 12:4616–4620

    Article  CAS  Google Scholar 

  • Montaner AD, Affanni JM, Park M, Fischer WH, Craig AG, Chang JP, Somoza GM, Rivier JE, Sherwood NM (2001) Primary structure of a novel gonadotropin-releasing hormone (GnRH) variant in the brain of pejerry (Odontesthes bonariensis). Endocrinology 142:1453–1460

    Article  PubMed  CAS  Google Scholar 

  • Montecucchi PC, Henschen A (1981) Amino acid composition and sequence analysis of sauvagine, a new active peptide from skin of Phyllomedusa sauvagei. Int J Pept Prot Res 18:113–120

    Article  CAS  Google Scholar 

  • Montecucchi PC, Gozzini L (1982) Secondary structure prediction of sauvagine, a novel biologically active polypeptide from a frog. Int J Pept Prot Res 20:139–143

    Article  CAS  Google Scholar 

  • Murthy ASN, Mains RE, Eipper BA (1986) Purification and characterization of peptidylglycine α-amidating monooxygenes from bovine neurointermediate pituitary. J Biol Chem 261:1815–1822

    PubMed  CAS  Google Scholar 

  • Ngamvongchon S, Lovejoy DA, Fischer WH, Craig AG, Nahorniak CS, Peter RE, Rivier JE, Sherwood NM (1992) Primary structures of two forms of gonadotropin-releasing hormone, one distinct and one conserved, from catfish brain. Mol Cell Neurosci 3:17–22

    Article  CAS  PubMed  Google Scholar 

  • Pallai PV, Mabilia M, Goodman M, Vale WW, Rivier JE (1983) Structural homology of corticotropin-releasing factor, sauvagine, and urotensin I: Circular dichroism and prediction studies. Proc Natl Acad Sci USA 80:6770–6774

    Article  PubMed  CAS  Google Scholar 

  • Pavlou SN, Brewer K, Farley MG, Lindner J, Bastias M-C, Rogers BJ, Rivier JE, Swift LL, Vale WW, Conn PM, Herbert CM (1991) Combined administration of a GnRH antagonist and testosterone in men induces reversible azoospermia without loss of libido. J Clin Endocrinol Metab 73:1360–1369

    PubMed  CAS  Google Scholar 

  • Podlech J, Seebach D (1995) On the preparation of b-amino acids from a-amino acids using the Arndt-Eistert reaction: Scope, limitations and stereoselectivity. Application to carbohydrate peptidation. Stereoselective α-alkylations of some b-amino acids. Liebigs Ann 1217–1228

    Google Scholar 

  • Powell JFF, Zohar Y, Elizur A, Park C, Fischer WH, Craig AG, Rivier JE, Lovejoy DA, Sherwood NM (1994) Three forms of gonadotropin-releasing hormone characterized from brains of one species. Proc Natl Acad Sci USA 91:12081–12085

    Article  PubMed  CAS  Google Scholar 

  • Powell JFF, Reska-Skinner SM, Prakash OM, Fischer WH, Park M, Rivier JE, Craig AG, Mackie GO, Sherwood NM (1996) Two new forms of gonadotropin-releasing hormone in a protochordate and the evolutionary implications. Proc Natl Acad Sci USA 93:10461–10464

    Article  PubMed  CAS  Google Scholar 

  • Pradayrol L, Jörnvall H, Mutt V, Ribet A (1980) N-terminally extended somatostatin: the primary structure of somatostatin-28. FEBS Lett 109:55–58

    Article  PubMed  CAS  Google Scholar 

  • Reubi JC, Schaer J-C, Wenger S, Hoeger C, Erchegyi J, Waser B, Rivier J (2000) SST3-selective potent peptidic somatostatin receptor antagonists. Proc Natl Acad Sci USA 97:13973–13978

    Article  PubMed  CAS  Google Scholar 

  • Reubi JC, Eisenwiener KP, Rink H, Waser B, Macke HR (2002) A new peptidic somatostatin agonist with high affinity to all five somatostatin receptors. Eur J Pharmacol 456:45–49

    Article  PubMed  CAS  Google Scholar 

  • Reyes TM, Lewis K, Perrin MH, Kunitake KS, Vaughan J, Arias CA, Hogenesch JB, Gulyas J, Rivier J, Vale WW, Sawchenko PE (2001) Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc Natl Acad Sci USA 98:2843–2848

    Article  PubMed  CAS  Google Scholar 

  • Rijkers DT, Kruijtzer JA, Van Oostenbrugge M, Ronken E, Den Hartog JA, Liskamp RM (2004) Structure-activity studies on the corticotropin releasing factor antagonist astressin, leading to a minimal sequence necessary for antagonistic activity. Chembiochem 5:340–348

    Article  PubMed  CAS  Google Scholar 

  • Rivier J, Spiess J, Thorner M, Vale W (1982) Characterization of a growth hormone releasing factor from a human pancreatic islet tumor. Nature 300:276–278

    Article  PubMed  CAS  Google Scholar 

  • Rivier J, Spiess J, Vale W (1983) Characterization of rat hypothalamic corticotropin-releasing factor. Proc Natl Acad Sci USA 80:4851–4855

    Article  PubMed  CAS  Google Scholar 

  • Rivier J, Rivier C, Vale W (1984) Synthetic competitive antagonists of corticotropin releasing factor: Effect on ACTH secretion in the rat. Science 224:889–891

    PubMed  CAS  Google Scholar 

  • Rivier J, Rivier C, Galyean R, Miranda A, Miller C, Craig AG, Yamamoto G, Brown M, Vale W (1993) Single point D-substituted corticotropin releasing factor analogues: Effects on potency and physicochemical characteristics. J Med Chem 36:2851–2859

    Article  PubMed  CAS  Google Scholar 

  • Rivier JE, Jiang G-C, Koerber SC, Porter J, Craig AG, Hoeger C (1996) Betidamino acids: Versatile and constrained scaffolds for drug discovery. Proc Natl Acad Sci USA 93:2031–2036

    Article  PubMed  CAS  Google Scholar 

  • Rivier J, Gulyas J, Corrigan A, Craig AG, Martinez V, Taché Y, Vale W, Rivier C (1998) Astressin analogues (CRF antagonists) with extended duration of action in the rat. J Med Chem 41:5012–5019

    Article  PubMed  CAS  Google Scholar 

  • Rivier JE, Struthers RS, Porter J, Lahrichi SL, Jiang G, Cervini LA, Ibea M, Kirby DA, Koerber SC, Rivier CL (2000) Design of potent dicyclic (4–10/5–8) gonadotropin releasing hormone (GnRH) antagonists. J Med Chem 43:784–796

    Article  PubMed  CAS  Google Scholar 

  • Rivier JE, Hoeger C, Erchegyi J, Gulyas J, DeBoard R, Craig AG, Koerber SC, Wenger S, Waser B, Schaer J-C, Reubi JC (2001a) Potent somatostatin undecapeptide agonists selective for somatostatin receptor 1 (sst1). J Med Chem 44:2238–2246

    Article  PubMed  CAS  Google Scholar 

  • Rivier JE, Gulyas J, Kirby D, Kunitake K, Donaldson C, Vaughan J, Perrin M, Koerber S, Martinez V, Taché Y, Rivier C, Vale W (2001b) Receptor-selective corticotropin releasing factor analogs. In: 31st Annual Meeting of the Society for Neuroscience: San Diego CA, Session number 413.417

    Google Scholar 

  • Rivier J, Gulyas J, Kirby D, Low W, Perrin MH, Kunitake K, DiGruccio M, Vaughan J, Reubi JC, Waser B, Koerber SC, Martínez V, Wang LX, Taché Y, Vale W (2002) Potent and long acting corticotropin releasing factor (CRF) receptor 2 selective peptide competitive antagonists. J Med Chem 45:4737–4747

    Article  PubMed  CAS  Google Scholar 

  • Rivier J, Erchegyi J, Hoeger C, Miller C, Low W, Wenger S, Waser B, Schaer J-C, Reubi JC (2003a) Novel sst4-selective somatostatin (SRIF) agonists. Part I: Lead identification using a betide scan. J Med Chem 46:5579–5586

    Article  PubMed  CAS  Google Scholar 

  • Rivier C, Grigoriadis D, Rivier J (2003b) Role of corticotropin-releasing factor receptors type 1 and 2 in modulating the rat ACTH response to stressors. Endocrinology 144:2396–2403

    Article  PubMed  CAS  Google Scholar 

  • Rohrer L, Raulf F, Bruns C, Buettner R, Hofstaedter F, Schule R (1993) Cloning and characterization of a fourth human somatostatin receptor. Proc Natl Acad Sci USA 90:4196–4200

    Article  PubMed  CAS  Google Scholar 

  • Sherwood N, Eiden L, Brownstein M, Spiess J, Rivier J, Vale W (1983) Characterization of a teleost gonadotropin-releasing hormone. Proc Natl Acad Sci USA 80:2794–2798

    Article  PubMed  CAS  Google Scholar 

  • Sherwood NM, Sower SA, Marshak DR, Fraser BA, Brownstein MJ (1986) Primary structure of gonadotropin-releasing hormone from lamprey brain. J Biol Chem 261:4812–4819

    PubMed  CAS  Google Scholar 

  • Shibahara S, Morimoto Y, Furutani Y, Notake M, Takahashi H, Shimizu S, Horikawa S, Numa S (1983) Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene. Embo J 2(5):775–779

    PubMed  CAS  Google Scholar 

  • Simon RJ, Kania RS, Zuckermann RN, Huebner VD, Jewell DA, Banville S, Ng S, Wang L, Rosenberg S, Marlowe CK, Spellmeyer DC, Tan R, Frankel AD, Santi DV, Cohen FE, Bartlett PA (1992) Peptoids: A modular approach to drug discovery. Proc Natl Acad Sci USA 89:9367–9371

    Article  PubMed  CAS  Google Scholar 

  • Sower SA, Chiang YC, Lovas S, Conlon JM (1993) Primary structure and biological activity of a third gonadotropin-releasing hormone from lamprey brain. Endocrinology 132:1125–1131

    Article  PubMed  CAS  Google Scholar 

  • Spatola AF (1983) Peptide backbone modifications: A structure-activity analysis of peptides containing amide bond surrogates, conformationl constraints, and related backbone replacements. In: Weinstein B (ed) Chemistry and biochemistry of amino acids, peptides and proteins. Marcel Dekker, New York, p 267–307

    Google Scholar 

  • Tezval H, Jahn O, Todorovic C, Sasse A, Eckart K, Spiess J (2004) Cortagine, a specific agonist of corticotropin-releasing factor receptor subtype 1, is anxiogenic and antidepressive in the mouse model. Proc Natl Acad Sci USA 101:9468–9473

    Article  PubMed  CAS  Google Scholar 

  • Vale W, Grant G, Amoss M, Blackwell R, Guillemin R (1972) Culture of enzymatically dispersed anterior pituitary cells. Functional validation of a method. Endocrinology 91:562–572

    Article  PubMed  CAS  Google Scholar 

  • Vale W, Rivier C, Brown M, Rivier J (1977) Pharmacology of TRF, LRF and somatostatin. In: Porter JC (ed) Hypothalamic peptide hormones and pituitary regulation: advances in experimental medicine and biology. Plenum Press, New York, p 123–156

    Google Scholar 

  • Vale W, Rivier C, Perrin M, Rivier J (1979) Synthetic peptides modulating the secretion of gonadotropins and reproductive functions. In: 6th American Peptide Symposium: Georgetown University, Washington, DC

    Google Scholar 

  • Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41 residue ovine hypothalamic peptide that stimulates the secretion of corticotropin and β-endorphin. Science 213:1394–1397

    PubMed  CAS  Google Scholar 

  • Vaughan JM, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull A, Lovejoy D, Rivier C, Rivier J, Sawchenko PE, Vale W (1995) Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 378:287–292

    Article  PubMed  CAS  Google Scholar 

  • Veber DF, Holly FW, Nutt RF, Bergstrand SJ, Brady SF, Hirschmann R, Glitzer MS, Saperstein R (1979) Highly active cyclic and bicyclic somatostatin analogues of reduced ring size. Nature 280:512–514

    Article  PubMed  CAS  Google Scholar 

  • Vickers ED, Laberge F, Adams BA, Hara TJ, Sherwood NM (2004) Cloning and localization of three forms of gonadotropin-releasing hormone, including the novel white fish form, in a salmonid, Coregonus clupeaformis. Biol Reprod 70:1136–1146

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Song H, Bruno JF, Berelowitz M (1993) Molecular cloning and sequencing of a human somatostatin receptor, hSSTR4. Biochem Biophys Res Commun 193:648–652

    Article  PubMed  CAS  Google Scholar 

  • Yamada Y, Reisine T, Law SF, Ihara Y, Kubota A, Kagimoto S, Seino M, Seino Y, Bell GI, Seino S (1992) Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. Mol Endocrinol 6:2136–2142

    Article  PubMed  CAS  Google Scholar 

  • Yamada Y, Kagimoto S, Kubota A, Yasuda K, Masuda K, Someya Y, Ihara Y, Li Q, Imura H, Seino S, Seino Y (1993)Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and fifth (hSSTR5) human somatostatin receptor subtype. Biochem Biophys Res Commun 195:844–852

    Article  PubMed  CAS  Google Scholar 

  • Yamada Y, Mizutani K, Mizusawa Y, Hantani Y, Tanaka M, Tanaka Y, Tomimoto M, Sugawara M, Imai N, Yamada H, Okajima N, Haruta J (2004) New class of corticotropin-releasing factor (CRF) antagonists: small peptides having high binding affinity for CRF receptor. J Med Chem 47:1075–1078

    Article  PubMed  CAS  Google Scholar 

  • Yasuda K, Rens-Domiano S, Breder C, Law SF, Saper C, Reisine T, Bell GI (1992) Cloning of a novel somatostatin receptor, SSTR3, coupled to adenylyl cyclase. J Biol Chem 267:20422–20428

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CA

    J. Rivier, J. Gulyas, J. Erchegyi, S. C. Koerber, M. DiGruccio, M. Perrin, C. Rivier & W. Vale

  2. Structural Biology Laboratory, The Salk Institute, La Jolla, CA

    C. R. R. Grace & R. Riek

  3. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland

    V. Eltschinger, B. Waser, R. Cescato & J. C. Reubi

Authors
  1. J. Rivier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Gulyas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Erchegyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. C. Koerber
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. R. R. Grace
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Riek
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. DiGruccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Perrin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. Rivier
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. V. Eltschinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. B. Waser
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. R. Cescato
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J. C. Reubi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. W. Vale
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Divisions of Neuroscience and Reproductive Biology, Departments of Physiology and Pharmacology and Cell and Developmental Biology, Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, Oregon, 97006, USA

    Michael Conn Ph.D.

  2. Institut Necker, 156, rue de Vaugirard, 75015, Paris, France

    Claude Kordon Ph.D.

  3. Pour la Recherche Thérapeutique, Fondation IPSEN, 24, rue Erlanger, 75781, Paris Cedex 16, France

    Yves Christen Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Rivier, J. et al. (2006). Guiding principles applied in the design of GPCR-selective hypothalamic hormone agonists and antagonists. In: Conn, M., Kordon, C., Christen, Y. (eds) Insights into Receptor Function and New Drug Development Targets. Research and Perspectives in Endocrine Interactions. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-34447-0_8

Download citation

Publish with us

Policies and ethics

Search

Navigation