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Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Mini-Review Article

Traceable Peptidic Ligands that Target Ghrelin Receptors

Author(s): Mengjie Liu, John Wade* and Mohammed Akhter Hossain*

Volume 21, Issue 10, 2020

Page: [955 - 964] Pages: 10

DOI: 10.2174/1389203721666200702131457

Price: $65

Abstract

Ghrelin is a 28-amino acid octanoylated peptide hormone that is implicated in many physiological and pathophysiological processes. Specific visualization of ghrelin and its cognate receptor using traceable ligands is crucial in elucidating the localization, functions, and expression pattern of the peptide’s signaling pathway. Here 12 representative radio- and fluorescently-labeled peptide-based ligands are reviewed for in vitro and in vivo imaging studies. In particular, the focus is on their structural features, pharmacological properties, and applications in further biochemical research.

Keywords: ghrelin, ghrelin receptor, peptide, radiolabeling, fluorescence, ligand.

Graphical Abstract

[1]
Kojima, M.; Hosoda, H.; Date, Y.; Nakazato, M.; Matsuo, H.; Kangawa, K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 1999, 402(6762), 656-660.
[http://dx.doi.org/10.1038/45230] [PMID: 10604470]
[2]
Sakata, I.; Yang, J.; Lee, C.E.; Osborne-Lawrence, S.; Rovinsky, S.A.; Elmquist, J.K.; Zigman, J.M. Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells. Am. J. Physiol. Endocrinol. Metab., 2009, 297(1), E134-E141.
[http://dx.doi.org/10.1152/ajpendo.90859.2008] [PMID: 19401456]
[3]
Korbonits, M.; Bustin, S.A.; Kojima, M.; Jordan, S.; Adams, E.F.; Lowe, D.G.; Kangawa, K.; Grossman, A.B. The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J. Clin. Endocrinol. Metab., 2001, 86(2), 881-887.
[http://dx.doi.org/10.1210/jc.86.2.881] [PMID: 11158061]
[4]
Volante, M.; Fulcheri, E.; Allìa, E.; Cerrato, M.; Pucci, A.; Papotti, M. Ghrelin expression in fetal, infant, and adult human lung. J. Histochem. Cytochem., 2002, 50(8), 1013-1021.
[http://dx.doi.org/10.1177/002215540205000803] [PMID: 12133904]
[5]
Mori, K.; Yoshimoto, A.; Takaya, K.; Hosoda, K.; Ariyasu, H.; Yahata, K.; Mukoyama, M.; Sugawara, A.; Hosoda, H.; Kojima, M.; Kangawa, K.; Nakao, K. Kidney produces a novel acylated peptide, ghrelin. FEBS Lett., 2000, 486(3), 213-216.
[http://dx.doi.org/10.1016/S0014-5793(00)02308-5] [PMID: 11119706]
[6]
Gualillo, O.; Caminos, J.; Blanco, M.; Garcìa-Caballero, T.; Kojima, M.; Kangawa, K.; Dieguez, C.; Casanueva, F. Ghrelin, a novel placental-derived hormone. Endocrinology, 2001, 142(2), 788-794.
[http://dx.doi.org/10.1210/endo.142.2.7987] [PMID: 11159851]
[7]
Gaytan, F.; Barreiro, M.L.; Caminos, J.E.; Chopin, L.K.; Herington, A.C.; Morales, C.; Pinilla, L.; Paniagua, R.; Nistal, M.; Casanueva, F.F.; Aguilar, E.; Diéguez, C.; Tena-Sempere, M. Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors. J. Clin. Endocrinol. Metab., 2004, 89(1), 400-409.
[http://dx.doi.org/10.1210/jc.2003-031375] [PMID: 14715878]
[8]
Gutierrez, J.A.; Solenberg, P.J.; Perkins, D.R.; Willency, J.A.; Knierman, M.D.; Jin, Z.; Witcher, D.R.; Luo, S.; Onyia, J.E.; Hale, J.E. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc. Natl. Acad. Sci. USA, 2008, 105(17), 6320-6325.
[http://dx.doi.org/10.1073/pnas.0800708105] [PMID: 18443287]
[9]
Yang, J.; Brown, M.S.; Liang, G.; Grishin, N.V.; Goldstein, J.L. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell, 2008, 132(3), 387-396.
[http://dx.doi.org/10.1016/j.cell.2008.01.017] [PMID: 18267071]
[10]
Kojima, M.; Kangawa, K. Ghrelin: structure and function. Physiol. Rev., 2005, 85(2), 495-522.
[http://dx.doi.org/10.1152/physrev.00012.2004] [PMID: 15788704]
[11]
Bednarek, M.A.; Feighner, S.D.; Pong, S-S.; McKee, K.K.; Hreniuk, D.L.; Silva, M.V.; Warren, V.A.; Howard, A.D.; Van Der Ploeg, L.H.Y.; Heck, J.V. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J. Med. Chem., 2000, 43(23), 4370-4376.
[http://dx.doi.org/10.1021/jm0001727] [PMID: 11087562]
[12]
Howard, A.D.; Feighner, S.D.; Cully, D.F.; Arena, J.P.; Liberator, P.A.; Rosenblum, C.I.; Hamelin, M.; Hreniuk, D.L.; Palyha, O.C.; Anderson, J.; Paress, P.S.; Diaz, C.; Chou, M.; Liu, K.K.; McKee, K.K.; Pong, S-S.; Chaung, L-Y.; Elbrecht, A.; Dashkevicz, M.; Heavens, R.; Rigby, M.; Sirinathsinghji, D.J.S.; Dean, D.C.; Melillo, D.G.; Patchett, A.A.; Nargund, R.; Griffin, P.R.; DeMartino, J.A.; Gupta, S.K.; Schaeffer, J.M.; Smith, R.G.; Van der Ploeg, L.H.T. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science, 1996, 273(5277), 974-977.
[http://dx.doi.org/10.1126/science.273.5277.974] [PMID: 8688086]
[13]
Gasco, V.; Beccuti, G.; Marotta, F.; Benso, A.; Granata, R.; Broglio, F.; Ghigo, E. Endocrine and Metabolic Actions of Ghrelin.Endocr. Dev; Loche, S.; Cappa, M.; Ghizzoni, L.; Maghnie, M; Savage, M.O., Ed.; Karger: Basel, 2010, Vol. 17, pp. 86-95.
[14]
Carreira, M.C.; Camiña, J.P.; Smith, R.G.; Casanueva, F.F. Agonist-specific coupling of growth hormone secretagogue receptor type 1a to different intracellular signaling systems. Role of adenosine. Neuroendocrinology, 2004, 79(1), 13-25.
[http://dx.doi.org/10.1159/000076042] [PMID: 14755130]
[15]
Ge, X.; Yang, H.; Bednarek, M.A.; Galon-Tilleman, H.; Chen, P.; Chen, M.; Lichtman, J.S.; Wang, Y.; Dalmas, O.; Yin, Y.; Tian, H.; Jermutus, L.; Grimsby, J.; Rondinone, C.M.; Konkar, A.; Kaplan, D.D. LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor. Cell Metab., 2018, 27(2), 461-469.e6.
[http://dx.doi.org/10.1016/j.cmet.2017.10.016] [PMID: 29233536]
[16]
Tschöp, M.; Smiley, D.L.; Heiman, M.L. Ghrelin induces adiposity in rodents. Nature, 2000, 407(6806), 908-913.
[http://dx.doi.org/10.1038/35038090] [PMID: 11057670]
[17]
Nakazato, M.; Murakami, N.; Date, Y.; Kojima, M.; Matsuo, H.; Kangawa, K.; Matsukura, S. A role for ghrelin in the central regulation of feeding. Nature, 2001, 409(6817), 194-198.
[http://dx.doi.org/10.1038/35051587] [PMID: 11196643]
[18]
Purtell, L.; Sze, L.; Loughnan, G.; Smith, E.; Herzog, H.; Sainsbury, A.; Steinbeck, K.; Campbell, L.V.; Viardot, A. In adults with Prader-Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels. Neuropeptides, 2011, 45(4), 301-307.
[http://dx.doi.org/10.1016/j.npep.2011.06.001] [PMID: 21722955]
[19]
Raghay, K.; Akki, R.; Bensaid, D.; Errami, M. Ghrelin as an anti-inflammatory and protective agent in ischemia/reperfusion injury. Peptides, 2020.124170226
[http://dx.doi.org/10.1016/j.peptides.2019.170226] [PMID: 31786283]
[20]
Yamashita, Y.; Makinodan, M.; Toritsuka, M.; Yamauchi, T.; Ikawa, D.; Kimoto, S.; Komori, T.; Takada, R.; Kayashima, Y.; Hamano-Iwasa, K.; Tsujii, M.; Matsuzaki, H.; Kishimoto, T. Anti-inflammatory Effect of Ghrelin in Lymphoblastoid Cell Lines From Children With Autism Spectrum Disorder. Front. Psychiatry, 2019, 10, 152.
[http://dx.doi.org/10.3389/fpsyt.2019.00152] [PMID: 30971960]
[21]
Kyoraku, I.; Shiomi, K.; Kangawa, K.; Nakazato, M. Ghrelin reverses experimental diabetic neuropathy in mice. Biochem. Biophys. Res. Commun., 2009, 389(3), 405-408.
[http://dx.doi.org/10.1016/j.bbrc.2009.08.171] [PMID: 19733151]
[22]
Qu, R.; Chen, X.; Hu, J.; Fu, Y.; Peng, J.; Li, Y.; Chen, J.; Li, P.; Liu, L.; Cao, J.; Wang, W.; Qiu, C.; Guo, L.; Vasilev, K.; Chen, J.; Zhou, G.; Li, W.; Zhao, Y. Ghrelin protects against contact dermatitis and psoriasiform skin inflammation by antagonizing TNF-α/NF-κB signaling pathways. Sci. Rep., 2019, 9(1), 1348.
[http://dx.doi.org/10.1038/s41598-018-38174-2] [PMID: 30718736]
[23]
Zhang, C.J.; Bidlingmaier, M.; Altaye, M.; Page, L.C.; D’Alessio, D.; Tschöp, M.H.; Tong, J. Acute administration of acyl, but not desacyl ghrelin, decreases blood pressure in healthy humans. Eur. J. Endocrinol., 2017, 176(2), 123-132.
[http://dx.doi.org/10.1530/EJE-16-0789] [PMID: 27913606]
[24]
Mao, Y.; Tokudome, T.; Kishimoto, I.; Otani, K.; Nishimura, H.; Yamaguchi, O.; Otsu, K.; Miyazato, M.; Kangawa, K. Endogenous ghrelin attenuates pressure overload-induced cardiac hypertrophy via a cholinergic anti-inflammatory pathway. Hypertension, 2015, 65(6), 1238-1244.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.04864] [PMID: 25870195]
[25]
Au, C.C.; Furness, J.B.; Brown, K.A. Ghrelin and Breast Cancer: Emerging Roles in Obesity, Estrogen Regulation, and Cancer. Front. Oncol., 2017, 6, 265.
[http://dx.doi.org/10.3389/fonc.2016.00265] [PMID: 28119851]
[26]
Lanfranco, F.; Baldi, M.; Cassoni, P.; Bosco, M.; Ghé, C.; Muccioli, G. Ghrelin and prostate cancer. Vitam. Horm., 2008, 77, 301-324.
[http://dx.doi.org/10.1016/S0083-6729(06)77013-3] [PMID: 17983862]
[27]
Soleyman-Jahi, S.; Sadeghi, F.; Pastaki Khoshbin, A.; Khani, L.; Roosta, V.; Zendehdel, K. Attribution of Ghrelin to Cancer; Attempts to Unravel an Apparent Controversy. Front. Oncol., 2019, 9, 1014.
[http://dx.doi.org/10.3389/fonc.2019.01014] [PMID: 31681567]
[28]
Lin, T-C.; Hsiao, M. Ghrelin and cancer progression. Biochim. Biophys. Acta Rev. Cancer, 2017, 1868(1), 51-57.
[http://dx.doi.org/10.1016/j.bbcan.2017.02.002] [PMID: 28238732]
[29]
Grönberg, M.; Ahlin, C.; Naeser, Y.; Janson, E.T.; Holmberg, L.; Fjällskog, M-L. Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer. PLoS One, 2017, 12(4)e0176059
[http://dx.doi.org/10.1371/journal.pone.0176059] [PMID: 28419141]
[30]
Pabalan, N.A.; Seim, I.; Jarjanazi, H.; Chopin, L.K. Associations between ghrelin and ghrelin receptor polymorphisms and cancer in Caucasian populations: a meta-analysis. BMC Genet., 2014, 15(1), 118.
[http://dx.doi.org/10.1186/s12863-014-0118-3] [PMID: 25376984]
[31]
Chen, C-Y.; Inui, A.; Asakawa, A.; Fujino, K.; Kato, I.; Chen, C-C.; Ueno, N.; Fujimiya, M. Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology, 2005, 129(1), 8-25.
[http://dx.doi.org/10.1053/j.gastro.2005.04.015] [PMID: 16012930]
[32]
Gauna, C.; Meyler, F.M.; Janssen, J.A.M.J.L.; Delhanty, P.J.D.; Abribat, T.; van Koetsveld, P.; Hofland, L.J.; Broglio, F.; Ghigo, E.; van der Lely, A.J. Administration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity. J. Clin. Endocrinol. Metab., 2004, 89(10), 5035-5042.
[http://dx.doi.org/10.1210/jc.2004-0363] [PMID: 15472202]
[33]
Delhanty, P.J.D.; Sun, Y.; Visser, J.A.; van Kerkwijk, A.; Huisman, M.; van Ijcken, W.F.J.; Swagemakers, S.; Smith, R.G.; Themmen, A.P.N.; van der Lely, A-J. Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice. PLoS One, 2010, 5(7)e11749
[http://dx.doi.org/10.1371/journal.pone.0011749] [PMID: 20668691]
[34]
Granata, R.; Settanni, F.; Biancone, L.; Trovato, L.; Nano, R.; Bertuzzi, F.; Destefanis, S.; Annunziata, M.; Martinetti, M.; Catapano, F.; Ghè, C.; Isgaard, J.; Papotti, M.; Ghigo, E.; Muccioli, G. Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic β-cells and human islets: involvement of 3′,5′-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling. Endocrinology, 2007, 148(2), 512-529.
[http://dx.doi.org/10.1210/en.2006-0266] [PMID: 17068144]
[35]
Granata, R.; Settanni, F.; Julien, M.; Nano, R.; Togliatto, G.; Trombetta, A.; Gallo, D.; Piemonti, L.; Brizzi, M.F.; Abribat, T.; van Der Lely, A-J.; Ghigo, E. Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats. J. Med. Chem., 2012, 55(6), 2585-2596.
[http://dx.doi.org/10.1021/jm201223m] [PMID: 22352743]
[36]
Moulin, A.; Ryan, J.; Martinez, J.; Fehrentz, J-A. Recent developments in ghrelin receptor ligands. ChemMedChem, 2007, 2(9), 1242-1259.
[http://dx.doi.org/10.1002/cmdc.200700015] [PMID: 17520591]
[37]
Chollet, C.; Meyer, K.; Beck-Sickinger, A.G. Ghrelin--a novel generation of anti-obesity drug: design, pharmacomodulation and biological activity of ghrelin analogues. J. Pept. Sci., 2009, 15(11), 711-730.
[http://dx.doi.org/10.1002/psc.1177] [PMID: 19787814]
[40]
Zollers, B.; Rhodes, L.; Heinen, E. Capromorelin oral solution (ENTYCE®) increases food consumption and body weight when administered for 4 consecutive days to healthy adult Beagle dogs in a randomized, masked, placebo controlled study. BMC Vet. Res., 2017, 13(1), 10.
[http://dx.doi.org/10.1186/s12917-016-0925-z] [PMID: 28056951]
[41]
Morozumi, N.; Hanada, T.; Habara, H.; Yamaki, A.; Furuya, M.; Nakatsuka, T.; Inomata, N.; Minamitake, Y.; Ohsuye, K.; Kangawa, K. The role of C-terminal part of ghrelin in pharmacokinetic profile and biological activity in rats. Peptides, 2011, 32(5), 1001-1007.
[http://dx.doi.org/10.1016/j.peptides.2011.01.021] [PMID: 21291937]
[42]
De Vriese, C.; Hacquebard, M.; Gregoire, F.; Carpentier, Y.; Delporte, C. Ghrelin interacts with human plasma lipoproteins. Endocrinology, 2007, 148(5), 2355-2362.
[http://dx.doi.org/10.1210/en.2006-1281] [PMID: 17289852]
[43]
Matsumoto, M.; Hosoda, H.; Kitajima, Y.; Morozumi, N.; Minamitake, Y.; Tanaka, S.; Matsuo, H.; Kojima, M.; Hayashi, Y.; Kangawa, K. Structure-activity relationship of ghrelin: pharmacological study of ghrelin peptides. Biochem. Biophys. Res. Commun., 2001, 287(1), 142-146.
[http://dx.doi.org/10.1006/bbrc.2001.5553] [PMID: 11549267]
[44]
Rosita, D.; Dewit, M.A.; Luyt, L.G. Fluorine and rhenium substituted ghrelin analogues as potential imaging probes for the growth hormone secretagogue receptor. J. Med. Chem., 2009, 52(8), 2196-2203.
[http://dx.doi.org/10.1021/jm8014519] [PMID: 19323558]
[45]
Maletínská, L.; Pýchová, M.; Holubová, M.; Blechová, M.; Demianová, Z.; Elbert, T.; Železná, B. Characterization of new stable ghrelin analogs with prolonged orexigenic potency. J. Pharmacol. Exp. Ther., 2012, 340(3), 781-786.
[http://dx.doi.org/10.1124/jpet.111.185371] [PMID: 22182933]
[46]
McGirr, R.; McFarland, M.S.; McTavish, J.; Luyt, L.G.; Dhanvantari, S. Design and characterization of a fluorescent ghrelin analog for imaging the growth hormone secretagogue receptor 1a. Regul. Pept., 2011, 172(1-3), 69-76.
[http://dx.doi.org/10.1016/j.regpep.2011.08.011] [PMID: 21893106]
[47]
Cabral, A.; Fernandez, G.; Perelló, M. Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid. Neuroscience, 2013, 253, 406-415.
[http://dx.doi.org/10.1016/j.neuroscience.2013.09.008] [PMID: 24042041]
[48]
Fernandez, G.; Cabral, A.; Andreoli, M.F.; Labarthe, A.; M’Kadmi, C.; Ramos, J.G.; Marie, J.; Fehrentz, J-A.; Epelbaum, J.; Tolle, V.; Perelló, M. Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice. Endocrinology, 2018, 159(2), 1021-1034.
[http://dx.doi.org/10.1210/en.2017-03101] [PMID: 29300858]
[49]
Cabral, A.; Portiansky, E.; Sánchez-Jaramillo, E.; Zigman, J.M.; Perelló, M. Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus. Psychoneuroendocrinology, 2016, 67, 27-39.
[http://dx.doi.org/10.1016/j.psyneuen.2016.01.027] [PMID: 26874559]
[50]
Lu, C.; McFarland, M.S.; Nesbitt, R-L.; Williams, A.K.; Chan, S.; Gomez-Lemus, J.; Autran-Gomez, A.M.; Al-Zahrani, A.; Chin, J.L.; Izawa, J.I.; Luyt, L.G.; Lewis, J.D. Ghrelin receptor as a novel imaging target for prostatic neoplasms. Prostate, 2012, 72(8), 825-833.
[http://dx.doi.org/10.1002/pros.21484] [PMID: 21919027]
[51]
Popovic, V.; Svetel, M.; Djurovic, M.; Petrovic, S.; Doknic, M.; Pekic, S.; Miljic, D.; Milic, N.; Glodic, J.; Dieguez, C.; Casanueva, F.F.; Kostic, V. Circulating and cerebrospinal fluid ghrelin and leptin: potential role in altered body weight in Huntington’s disease. Eur. J. Endocrinol., 2004, 151(4), 451-455.
[http://dx.doi.org/10.1530/eje.0.1510451] [PMID: 15476444]
[52]
Uriarte, M.; De Francesco, P.N.; Fernandez, G.; Cabral, A.; Castrogiovanni, D.; Lalonde, T.; Luyt, L.G.; Trejo, S.; Perelló, M. Evidence Supporting a Role for the Blood-Cerebrospinal Fluid Barrier Transporting Circulating Ghrelin into the Brain. Mol. Neurobiol., 2019, 56(6), 4120-4134.
[http://dx.doi.org/10.1007/s12035-018-1362-8] [PMID: 30276663]
[53]
Lufrano, D.; Trejo, S.A.; Llovera, R.E.; Salgueiro, M.; Fernandez, G.; Martínez Damonte, V.; González Flecha, F.L.; Raingo, J.; Ermácora, M.R.; Perelló, M. Ghrelin binding to serum albumin and its biological impact. Mol. Cell. Endocrinol., 2016, 436, 130-140.
[http://dx.doi.org/10.1016/j.mce.2016.07.016] [PMID: 27431015]
[54]
Douglas, G.A.F.; McGirr, R.; Charlton, C.L.; Kagan, D.B.; Hoffman, L.M.; Luyt, L.G.; Dhanvantari, S. Characterization of a far-red analog of ghrelin for imaging GHS-R in P19-derived cardiomyocytes. Peptides, 2014, 54, 81-88.
[http://dx.doi.org/10.1016/j.peptides.2014.01.011] [PMID: 24468548]
[55]
Charron, C.L.; McFarland, M.S.; Dhanvantari, S.; Luyt, L.G. Development of a [68Ga]-ghrelin analogue for PET imaging of the ghrelin receptor (GHS-R1a). MedChemComm, 2018, 9(10), 1761-1767.
[http://dx.doi.org/10.1039/C8MD00210J] [PMID: 30429981]
[56]
Murrell, E.; Kovacs, M.S.; Luyt, L.G. A Compact and Synthetically Accessible Fluorine-18 Labelled Cyclooctyne Prosthetic Group for Labelling of Biomolecules by Copper-Free Click Chemistry. ChemMedChem, 2018, 13(16), 1625-1628.
[http://dx.doi.org/10.1002/cmdc.201800334] [PMID: 29923326]
[57]
Bigott-Hennkens, H.M.; Junnotula, S.; Ma, L.; Gallazzi, F.; Lewis, M.R.; Jurisson, S.S. Synthesis and in vitro evaluation of a rhenium-cyclized somatostatin derivative series. J. Med. Chem., 2008, 51(5), 1223-1230.
[http://dx.doi.org/10.1021/jm701056x] [PMID: 18269231]
[58]
Giblin, M.F.; Wang, N.; Hoffman, T.J.; Jurisson, S.S.; Quinn, T.P. Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination. Proc. Natl. Acad. Sci. USA, 1998, 95(22), 12814-12818.
[http://dx.doi.org/10.1073/pnas.95.22.12814] [PMID: 9788997]
[59]
Charron, C.L.; Hou, J.; McFarland, M.S.; Dhanvantari, S.; Kovacs, M.S.; Luyt, L.G. Structure-Activity Study of Ghrelin(1-8) Resulting in High Affinity Fluorine-Bearing Ligands for the Ghrelin Receptor. J. Med. Chem., 2017, 60(17), 7256-7266.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00164] [PMID: 28719746]
[60]
Lalonde, T.; Shepherd, T.G.; Dhanvantari, S.; Luyt, L.G. Stapled Ghrelin Peptides as Fluorescent Imaging Probes. Pept. Sci., 2019, 111(1)e24055
[http://dx.doi.org/10.1002/pep2.24055]
[61]
Elias, K.A.; Ingle, G.S.; Burnier, J.P.; Hammonds, R.G.; McDowell, R.S.; Rawson, T.E.; Somers, T.C.; Stanley, M.S.; Cronin, M.J. In vitro characterization of four novel classes of growth hormone-releasing peptide. Endocrinology, 1995, 136(12), 5694-5699.
[http://dx.doi.org/10.1210/endo.136.12.7588325] [PMID: 7588325]
[62]
Somers, T. C.; Elias, K. A.; Clark, R. G.; Mcdowell, R. S.; Stanley, M. S.; Burnier, J. P.; Rawson, T. E. Low Molecular Weight Peptidomimetic Growth Hormone Secretagogues. WO1996015148A2,. 1996.
[63]
Fowkes, M.M. Peptidomimetic GHS-R1a Agonists as PET Imaging Agents for Prostate Cancer.. Electronic Thesis and Dissertation Repository, 2014, 1972..
[64]
Fowkes, M.M.; Lalonde, T.; Yu, L.; Dhanvantari, S.; Kovacs, M.S.; Luyt, L.G. Peptidomimetic growth hormone secretagogue derivatives for positron emission tomography imaging of the ghrelin receptor. Eur. J. Med. Chem., 2018, 157, 1500-1511.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.062] [PMID: 30282322]
[65]
Abbas, A.; Yu, L.; Lalonde, T.; Wu, D.; Thiessen, J.D.; Luyt, L.G.; Dhanvantari, S. Development and Characterization of an 18F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor. Mol. Imaging, 2018, 171536012118809587
[http://dx.doi.org/10.1177/1536012118809587] [PMID: 30394854]
[66]
Lalonde, T.; Fowkes, M.M.; Hou, J.; Thibeault, P.E.; Milne, M.; Dhanvantari, S.; Ramachandran, R.; Luyt, L.G. Single Amino Acid Replacement in G-7039 Leads to a 70-fold Increase in Binding toward GHS-R1a. ChemMedChem, 2019, 14(20), 1762-1766.
[http://dx.doi.org/10.1002/cmdc.201900466] [PMID: 31469937]
[67]
Holst, B.; Cygankiewicz, A.; Jensen, T.H.; Ankersen, M.; Schwartz, T.W. High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist. Mol. Endocrinol., 2003, 17(11), 2201-2210.
[http://dx.doi.org/10.1210/me.2003-0069] [PMID: 12907757]
[68]
Chollet, C.; Bergmann, R.; Pietzsch, J.; Beck-Sickinger, A.G. Design, evaluation, and comparison of ghrelin receptor agonists and inverse agonists as suitable radiotracers for PET imaging. Bioconjug. Chem., 2012, 23(4), 771-784.
[http://dx.doi.org/10.1021/bc2005889] [PMID: 22372770]
[69]
Barrile, F.; M’Kadmi, C.; De Francesco, P.N.; Cabral, A.; García Romero, G.; Mustafá, E.R.; Cantel, S.; Damian, M.; Mary, S.; Denoyelle, S.; Banères, J-L.; Marie, J.; Raingo, J.; Fehrentz, J-A.; Perelló, M. Development of a novel fluorescent ligand of growth hormone secretagogue receptor based on the N-Terminal Leap2 region. Mol. Cell. Endocrinol., 2019, 498110573
[http://dx.doi.org/10.1016/j.mce.2019.110573] [PMID: 31499133]
[70]
M’Kadmi, C.; Cabral, A.; Barrile, F.; Giribaldi, J.; Cantel, S.; Damian, M.; Mary, S.; Denoyelle, S.; Dutertre, S.; Péraldi-Roux, S.; Neasta, J.; Oiry, C.; Banères, J-L.; Marie, J.; Perelló, M.; Fehrentz, J-A. N-Terminal Liver-Expressed Antimicrobial Peptide 2 (LEAP2) Region Exhibits Inverse Agonist Activity toward the Ghrelin Receptor. J. Med. Chem., 2019, 62(2), 965-973.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01644] [PMID: 30543423]
[71]
Fernandez, G.; Cabral, A.; Cornejo, M.P.; De Francesco, P.N.; Garcia-Romero, G.; Reynaldo, M.; Perello, M. Des-Acyl Ghrelin Directly Targets the Arcuate Nucleus in a Ghrelin-Receptor Independent Manner and Impairs the Orexigenic Effect of Ghrelin. J. Neuroendocrinol., 2016, 28(2), 12349.
[http://dx.doi.org/10.1111/jne.12349] [PMID: 26661382]

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