ACS Publications. Most Trusted. Most Cited. Most Read

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:Biochemistry 2006, 45, 3, 1043-1053
RETURN TO ISSUEPREVArticleNEXT

Relaxin-3:  Improved Synthesis Strategy and Demonstration of Its High-Affinity Interaction with the Relaxin Receptor LGR7 Both In Vitro and In Vivo†

View Author Information
Howard Florey Institute, University of Melbourne, Melbourne, Victoria 3010, Australia, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, and BresaGen Ltd., Post Office Box 259 Rundle Mall, Adelaide, South Australia 5000, Australia
Cite this: Biochemistry 2006, 45, 3, 1043–1053
Publication Date (Web):December 22, 2005
https://doi.org/10.1021/bi052233e
Copyright © 2006 American Chemical Society
Request reuse permissions

    Article Views

    1034

    Altmetric

    -

    Citations

    128
    LEARN ABOUT THESE METRICS
    Read OnlinePDF (310 KB)
    Get e-Alerts
    SUBJECTS:

    Abstract

    Abstract Image

    Relaxin-3 is a member of the human relaxin peptide family, the gene for which, RLN3, is predominantly expressed in the brain. Mapping studies in the rodent indicate a highly developed network of RLN3, RLN1, and relaxin receptor-expressing cells in the brain, suggesting that relaxin peptides have important functional roles in the central nervous system. A regioselective disulfide-bond synthesis protocol was developed and used for the chemical synthesis of human (H3) relaxin-3. The selectively S-protected A and B chains were combined by stepwise formation of each of the three insulin-like disulfides via aeration, thioloysis, and iodolysis. Judicious positioning of the three sets of S-protecting groups was crucial for acquisition of synthetic H3 relaxin in a good overall yield. The activity of the peptide was tested against relaxin family peptide receptors. Although the highest activity was demonstrated on the human relaxin-3 receptor (GPCR135), the peptide also showed high activity on relaxin receptors (LGR7) from various species and variable activity on the INSL3 receptor (LGR8). Recombinant mouse prorelaxin-3 demonstrated similar activity to H3 relaxin, suggesting that the presence of the C peptide did not influence the conformation of the active site. H3 relaxin was also able to activate native LGR7 receptors. It stimulated increased MMP-2 expression in LGR7-expressing rat ventricular fibroblasts in a dose-dependent manner and, following infusion into the lateral ventricle of the brain, stimulated water drinking in rats, activating LGR7 receptors located in the subfornical organ. Thus, H3 relaxin is able to interact with the relaxin receptor LGR7 both in vitro and in vivo.

    †

     This work was supported by an Institute Block Grant (reg. key 983001) from the NHMRC to the Howard Florey Institute and by NHMRC Project Grants (350284 and 30012) to J.D.W., R.A.D.B., and G.W.T.

    ‡

     Howard Florey Institute, University of Melbourne.

    §

     The Wistar Institute.

    ‖

     BresaGen Ltd.

    *

     To whom correspondence should be addressed:  Howard Florey Institute, University of Melbourne, Melbourne, Victoria 3010, Australia. Telephone:  +61-3-8344-7285. Fax:  +61-3-9348-1707. E-mail: [email protected].

    Cited By

    This article is cited by 128 publications.

    1. Ross A. D. Bathgate, Praveen Praveen, Ashish Sethi, Werner I. Furuya, Rishi R. Dhingra, Martina Kocan, Qinghao Ou, Adam L. Valkovic, Isis Gil-Miravet, Mónica Navarro-Sánchez, Francisco E. Olucha-Bordonau, Andrew L. Gundlach, K. Johan Rosengren, Paul R. Gooley, Mathias Dutschmann, Mohammed Akhter Hossain. Noncovalent Peptide Stapling Using Alpha-Methyl-l-Phenylalanine for α-Helical Peptidomimetics. Journal of the American Chemical Society 2023, 145 (37) , 20242-20247. https://doi.org/10.1021/jacs.3c02743
    2. Mohammed Akhter Hossain, Praveen Praveen, Nurhayati Ahmad Noorzi, Hongkang Wu, Ian P. Harrison, Thomas Handley, Stavros Selemidis, Chrishan S. Samuel, Ross A. D. Bathgate. Development of Novel High-Affinity Antagonists for the Relaxin Family Peptide Receptor 1. ACS Pharmacology & Translational Science 2023, 6 (5) , 842-853. https://doi.org/10.1021/acsptsci.3c00053
    3. Mohammed Akhter Hossain and John D. Wade . Novel Methods for the Chemical Synthesis of Insulin Superfamily Peptides and of Analogues Containing Disulfide Isosteres. Accounts of Chemical Research 2017, 50 (9) , 2116-2127. https://doi.org/10.1021/acs.accounts.7b00288
    4. Fa Liu, Pengyun Li, Vasily Gelfanov, John Mayer, and Richard DiMarchi . Synthetic Advances in Insulin-like Peptides Enable Novel Bioactivity. Accounts of Chemical Research 2017, 50 (8) , 1855-1865. https://doi.org/10.1021/acs.accounts.7b00227
    5. Xu Yang, Vasily Gelfanov, Fa Liu, and Richard DiMarchi . Synthetic Route to Human Relaxin-2 via Iodine-Free Sequential Disulfide Bond Formation. Organic Letters 2016, 18 (21) , 5516-5519. https://doi.org/10.1021/acs.orglett.6b02751
    6. Keiko Hojo, Mohammed Akhter Hossain, Julien Tailhades, Fazel Shabanpoor, Lilian L. L. Wong, Emma E. K. Ong-Pålsson, Hanna E. Kastman, Sherie Ma, Andrew L. Gundlach, K. Johan Rosengren, John D. Wade, and Ross A. D. Bathgate . Development of a Single-Chain Peptide Agonist of the Relaxin-3 Receptor Using Hydrocarbon Stapling. Journal of Medicinal Chemistry 2016, 59 (16) , 7445-7456. https://doi.org/10.1021/acs.jmedchem.6b00265
    7. Linda M. Haugaard-Kedström, Mohammed Akhter Hossain, Norelle L. Daly, Ross A. D. Bathgate, Ernst Rinderknecht, John D. Wade, David J. Craik, and K. Johan Rosengren . Solution Structure, Aggregation Behavior, and Flexibility of Human Relaxin-2. ACS Chemical Biology 2015, 10 (3) , 891-900. https://doi.org/10.1021/cb500918v
    8. Fa Liu, Qingyuan Liu, and Adam R. Mezo . An Iodine-Free and Directed-Disulfide-Bond-Forming Route to Insulin Analogues. Organic Letters 2014, 16 (11) , 3126-3129. https://doi.org/10.1021/ol501252b
    9. Alessia Belgi, Mohammed A. Hossain, Fazel Shabanpoor, Linda Chan, Suode Zhang, Ross A. D. Bathgate, Geoffrey W. Tregear, and John D. Wade . Structure and Function Relationship of Murine Insulin-like Peptide 5 (INSL5): Free C-Terminus Is Essential for RXFP4 Receptor Binding and Activation. Biochemistry 2011, 50 (39) , 8352-8361. https://doi.org/10.1021/bi201093m
    10. Linda M. Haugaard-Kedström, Fazel Shabanpoor, Mohammed Akhter Hossain, Richard J. Clark, Philip J. Ryan, David J. Craik, Andrew L. Gundlach, John D. Wade, Ross A. D. Bathgate, and K. Johan Rosengren . Design, Synthesis, and Characterization of a Single-Chain Peptide Antagonist for the Relaxin-3 Receptor RXFP3. Journal of the American Chemical Society 2011, 133 (13) , 4965-4974. https://doi.org/10.1021/ja110567j
    11. Mohammed Akhter Hossain, Bryna Chow Suet Man, Chongxin Zhao, Qi Xu, Xiao-Jun Du, John D. Wade, and Chrishan S. Samuel . H3 Relaxin Demonstrates Antifibrotic Properties via the RXFP1 Receptor. Biochemistry 2011, 50 (8) , 1368-1375. https://doi.org/10.1021/bi1013968
    12. Mohammed Akhter Hossain, Alessia Belgi, Feng Lin, Suode Zhang, Fazel Shabanpoor, Linda Chan, Chris Belyea, Hue-Trung Truong, Amy R. Blair, Sof Andrikopoulos, Geoffrey W. Tregear and John D. Wade . Use of a Temporary “Solubilizing” Peptide Tag for the Fmoc Solid-Phase Synthesis of Human Insulin Glargine via Use of Regioselective Disulfide Bond Formation. Bioconjugate Chemistry 2009, 20 (7) , 1390-1396. https://doi.org/10.1021/bc900181a
    13. Chrishan S. Samuel,, Feng Lin,, Mohammed Akhter Hossain,, Chongxin Zhao,, Tania Ferraro,, Ross A. D. Bathgate,, Geoffrey W. Tregear, and, John D. Wade. Improved Chemical Synthesis and Demonstration of the Relaxin Receptor Binding Affinity and Biological Activity of Mouse Relaxin. Biochemistry 2007, 46 (18) , 5374-5381. https://doi.org/10.1021/bi700238h
    14. Duan Chen, Jens F. Rehfeld, Alan G. Watts, Patrik Rorsman, Andrew L. Gundlach. History of key regulatory peptide systems and perspectives for future research. Journal of Neuroendocrinology 2023, 35 (11) https://doi.org/10.1111/jne.13251
    15. Chrishan S. Samuel, Robert G. Bennett. Relaxin as an anti-fibrotic treatment: Perspectives, challenges and future directions. Biochemical Pharmacology 2022, 197 , 114884. https://doi.org/10.1016/j.bcp.2021.114884
    16. Richard J. Spears, Clíona McMahon, Vijay Chudasama. Cysteine protecting groups: applications in peptide and protein science. Chemical Society Reviews 2021, 50 (19) , 11098-11155. https://doi.org/10.1039/D1CS00271F
    17. Hoai Buu Ngo, Mariana R. Melo, Sharon Layfield, Angela A. Connelly, Jaspreet K. Bassi, Lin Xie, Clément Menuet, Stuart J. McDougall, Ross A.D. Bathgate, Andrew M. Allen. A Chemogenetic Tool that Enables Functional Neural Circuit Analysis. Cell Reports 2020, 32 (11) , 108139. https://doi.org/10.1016/j.celrep.2020.108139
    18. Rongjun He, Jia Pan, John P. Mayer, Fa Liu. Stepwise Construction of Disulfides in Peptides. ChemBioChem 2020, 21 (8) , 1101-1111. https://doi.org/10.1002/cbic.201900717
    19. Praveen Praveen, Ross A. D. Bathgate, Mohammed Akhter Hossain. Engineering of chimeric peptides as antagonists for the G protein-coupled receptor, RXFP4. Scientific Reports 2019, 9 (1) https://doi.org/10.1038/s41598-019-53707-z
    20. Brian DeChristopher, Soo-Hee Park, Linh Vong, Derek Bamford, Hyun-Hee Cho, Rohit Duvadie, Allison Fedolak, Christopher Hogan, Toshiyuki Honda, Pramod Pandey, Olga Rozhitskaya, Liansheng Su, Elizabeth Tomlinson, Iain Wallace. Discovery of a small molecule RXFP3/4 agonist that increases food intake in rats upon acute central administration. Bioorganic & Medicinal Chemistry Letters 2019, 29 (8) , 991-994. https://doi.org/10.1016/j.bmcl.2019.02.013
    21. Mouna Haidar, Kimberly Tin, Cary Zhang, Mohsen Nategh, João Covita, Alexander D. Wykes, Jake Rogers, Andrew L. Gundlach. Septal GABA and Glutamate Neurons Express RXFP3 mRNA and Depletion of Septal RXFP3 Impaired Spatial Search Strategy and Long-Term Reference Memory in Adult Mice. Frontiers in Neuroanatomy 2019, 13 https://doi.org/10.3389/fnana.2019.00030
    22. Kenta Arai, Toshiki Takei, Reina Shinozaki, Masato Noguchi, Shouta Fujisawa, Hidekazu Katayama, Luis Moroder, Setsuko Ando, Masaki Okumura, Kenji Inaba, Hironobu Hojo, Michio Iwaoka. Characterization and optimization of two-chain folding pathways of insulin via native chain assembly. Communications Chemistry 2018, 1 (1) https://doi.org/10.1038/s42004-018-0024-0
    23. Xiaohua You, Zhi-Fu Guo, Fang Cheng, Bing Yi, Fan Yang, Xinzhu Liu, Ni Zhu, Xianxian Zhao, Guijun Yan, Xin-Liang Ma, Jianxin Sun. Transcriptional up-regulation of relaxin-3 by Nur77 attenuates β-adrenergic agonist–induced apoptosis in cardiomyocytes. Journal of Biological Chemistry 2018, 293 (36) , 14001-14011. https://doi.org/10.1074/jbc.RA118.003099
    24. S. Hanafy, J. H. Sabry, E. M. Akl, R. A. Elethy, T. Mostafa. Serum relaxin-3 hormone relationship to male delayed puberty. Andrologia 2018, 50 (2) , e12882. https://doi.org/10.1111/and.12882
    25. Roger J. Summers, Michelle L. Halls, Ross A. D. Bathgate. Relaxin Family Peptide Receptors RXFP1 and RXFP2. 2018, 4583-4615. https://doi.org/10.1007/978-3-319-67199-4_362
    26. Camila de Ávila, Sandrine Chometton, Christophe Lenglos, Juliane Calvez, Andrew L. Gundlach, Elena Timofeeva. Differential effects of relaxin-3 and a selective relaxin-3 receptor agonist on food and water intake and hypothalamic neuronal activity in rats. Behavioural Brain Research 2018, 336 , 135-144. https://doi.org/10.1016/j.bbr.2017.08.044
    27. Loggan Malone, Juan C. Opazo, Peter L. Ryan, Federico G. Hoffmann. Progressive erosion of the Relaxin1 gene in bovids. General and Comparative Endocrinology 2017, 252 , 12-17. https://doi.org/10.1016/j.ygcen.2017.07.011
    28. Marta Nowak, Aykut Gram, Alois Boos, Selim Aslan, Serhan S Ay, Firdevs Önyay, Mariusz P Kowalewski. Functional implications of the utero-placental relaxin (RLN) system in the dog throughout pregnancy and at term. Reproduction 2017, 154 (4) , 415-431. https://doi.org/10.1530/REP-17-0135
    29. Kishore Thalluri, Binbin Kou, Xu Yang, Alexander N. Zaykov, John P. Mayer, Vasily M. Gelfanov, Fa Liu, Richard D. DiMarchi. Synthesis of relaxin‐2 and insulin‐like peptide 5 enabled by novel tethering and traceless chemical excision. Journal of Peptide Science 2017, 23 (6) , 455-465. https://doi.org/10.1002/psc.3010
    30. C. Zhang, D. V. Baimoukhametova, C. M. Smith, J. S. Bains, Andrew L. Gundlach. Relaxin-3/RXFP3 signalling in mouse hypothalamus: no effect of RXFP3 activation on corticosterone, despite reduced presynaptic excitatory input onto paraventricular CRH neurons in vitro. Psychopharmacology 2017, 234 (11) , 1725-1739. https://doi.org/10.1007/s00213-017-4575-z
    31. M. Haidar, G. Guèvremont, C. Zhang, R.A.D. Bathgate, E. Timofeeva, C.M. Smith, A.L. Gundlach. Relaxin‐3 inputs target hippocampal interneurons and deletion of hilar relaxin‐3 receptors in “floxed‐RXFP3” mice impairs spatial memory. Hippocampus 2017, 27 (5) , 529-546. https://doi.org/10.1002/hipo.22709
    32. Juliane Calvez, Camila de Ávila, Elena Timofeeva. Sex‐specific effects of relaxin‐3 on food intake and body weight gain. British Journal of Pharmacology 2017, 174 (10) , 1049-1060. https://doi.org/10.1111/bph.13530
    33. Sherie Ma, Craig M Smith, Anna Blasiak, Andrew L Gundlach. Distribution, physiology and pharmacology of relaxin‐3/RXFP3 systems in brain. British Journal of Pharmacology 2017, 174 (10) , 1034-1048. https://doi.org/10.1111/bph.13659
    34. Nitin A Patil, K Johan Rosengren, Frances Separovic, John D Wade, Ross A D Bathgate, Mohammed Akhter Hossain. Relaxin family peptides: structure–activity relationship studies. British Journal of Pharmacology 2017, 174 (10) , 950-961. https://doi.org/10.1111/bph.13684
    35. Richard Ivell, Alexander I Agoulnik, Ravinder Anand‐Ivell. Relaxin‐like peptides in male reproduction – a human perspective. British Journal of Pharmacology 2017, 174 (10) , 990-1001. https://doi.org/10.1111/bph.13689
    36. Sheng Y. Ang, Dana S. Hutchinson, Bronwyn A. Evans, Mohammed A. Hossain, Nitin Patil, Ross A. D. Bathgate, Martina Kocan, Roger J. Summers. The actions of relaxin family peptides on signal transduction pathways activated by the relaxin family peptide receptor RXFP4. Naunyn-Schmiedeberg's Archives of Pharmacology 2017, 390 (1) , 105-111. https://doi.org/10.1007/s00210-016-1321-8
    37. M.L. Halls. Insulin-Like Peptide 3 (INSL3) ☆. 2017https://doi.org/10.1016/B978-0-12-801238-3.99369-3
    38. Tharindunee Jayakody, Subhi Marwari, Rajamani Lakshminarayanan, Francis Chee Kuan Tan, Charles William Johannes, Brian William Dymock, Anders Poulsen, Deron Raymond Herr, Gavin Stewart Dawe. Hydrocarbon stapled B chain analogues of relaxin-3 retain biological activity. Peptides 2016, 84 , 44-57. https://doi.org/10.1016/j.peptides.2016.08.001
    39. Fangzhou Wu, John P. Mayer, Alexander N. Zaykov, Fa Zhang, Fa Liu, Richard D. DiMarchi. Chemical Synthesis of Human Insulin‐Like Peptide‐6. Chemistry – A European Journal 2016, 22 (28) , 9777-9783. https://doi.org/10.1002/chem.201601410
    40. Fa Liu, Alexander N. Zaykov, Jay J. Levy, Richard D. DiMarchi, John P. Mayer. Chemical synthesis of peptides within the insulin superfamily. Journal of Peptide Science 2016, 22 (5) , 260-270. https://doi.org/10.1002/psc.2863
    41. Qing-Ping Wu, Lei Zhang, Xiao-Xia Shao, Jia-Hui Wang, Yu Gao, Zeng-Guang Xu, Ya-Li Liu, Zhan-Yun Guo. Application of the novel bioluminescent ligand–receptor binding assay to relaxin-RXFP1 system for interaction studies. Amino Acids 2016, 48 (4) , 1099-1107. https://doi.org/10.1007/s00726-015-2146-3
    42. Mouna Haidar, Monica Lam, Berenice E. Chua, Craig M. Smith, Andrew L. Gundlach. Sensitivity to Chronic Methamphetamine Administration and Withdrawal in Mice with Relaxin-3/RXFP3 Deficiency. Neurochemical Research 2016, 41 (3) , 481-491. https://doi.org/10.1007/s11064-015-1621-2
    43. Jasinda H. Lee, Shu Qing Koh, Simone Guadagna, Paul T. Francis, Margaret M. Esiri, Christopher P. Chen, Peter T.-H. Wong, Gavin S. Dawe, Mitchell K. P. Lai. Altered relaxin family receptors RXFP1 and RXFP3 in the neocortex of depressed Alzheimer’s disease patients. Psychopharmacology 2016, 233 (4) , 591-598. https://doi.org/10.1007/s00213-015-4131-7
    44. L. H. C. Assis, D. Crespo, R. D. V. S. Morais, L. R. França, J. Bogerd, R. W. Schulz. INSL3 stimulates spermatogonial differentiation in testis of adult zebrafish (Danio rerio). Cell and Tissue Research 2016, 363 (2) , 579-588. https://doi.org/10.1007/s00441-015-2213-9
    45. Roger J. Summers, Michelle L. Halls, Ross A. D. Bathgate. Relaxin Family Peptide Receptors RXFP1 and RXFP2. 2016, 1-32. https://doi.org/10.1007/978-1-4614-6438-9_362-1
    46. Craig M. Smith, Lesley L. Walker, Berenice E. Chua, Michael J. McKinley, Andrew L. Gundlach, Derek A. Denton, Andrew J. Lawrence. Involvement of central relaxin‐3 signalling in sodium (salt) appetite. Experimental Physiology 2015, 100 (9) , 1064-1072. https://doi.org/10.1113/EP085349
    47. Michelle L. Halls, Ross A. D. Bathgate, Steve W. Sutton, Thomas B. Dschietzig, Roger J. Summers, . International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides. Pharmacological Reviews 2015, 67 (2) , 389-440. https://doi.org/10.1124/pr.114.009472
    48. Ihaia T. Hosken, Steven W. Sutton, Craig M. Smith, Andrew L. Gundlach. Relaxin-3 receptor (Rxfp3) gene knockout mice display reduced running wheel activity: Implications for role of relaxin-3/RXFP3 signalling in sustained arousal. Behavioural Brain Research 2015, 278 , 167-175. https://doi.org/10.1016/j.bbr.2014.09.028
    49. Lindsay H. Bergeron, Jordan M. Willcox, Faisal J. Alibhai, Barry J. Connell, Tarek M. Saleh, Brian C. Wilson, Alastair J. S. Summerlee. Relaxin Peptide Hormones Are Protective During the Early Stages of Ischemic Stroke in Male Rats. Endocrinology 2015, 156 (2) , 638-646. https://doi.org/10.1210/en.2014-1676
    50. Lisbeth Kristensson, Gaëll Mayer, Karolina Ploj, Martina Wetterlund, Susanne Arlbrandt, Anna Björquist, Britt-Marie Wissing, Marie Castaldo, Niklas Larsson. Partial agonist activity of R3(BΔ23–27)R/I5 at RXFP3 – Investigation of in vivo and in vitro pharmacology. European Journal of Pharmacology 2015, 747 , 123-131. https://doi.org/10.1016/j.ejphar.2014.11.041
    51. Thomas Bernd Dschietzig, Katharina Krause-Relle, Maud Hennequin, Karoline von Websky, Jan Rahnenführer, Jana Ruppert, Hans Jürgen Grön, Franz Paul Armbruster, Ross A. D. Bathgate, Joerg R. Aschenbach, Wolf-Georg Forssmann, Berthold Hocher. Relaxin-2 Does Not Ameliorate Nephropathy in an Experimental Model of Type-1 Diabetes. Kidney and Blood Pressure Research 2015, 40 (1) , 77-88. https://doi.org/10.1159/000368484
    52. Mohammed Akhter Hossain, John D Wade. Synthetic relaxins. Current Opinion in Chemical Biology 2014, 22 , 47-55. https://doi.org/10.1016/j.cbpa.2014.09.014
    53. Carolina Duarte, Yukiho Kobayashi, Tatsuo Kawamoto, Keiji Moriyama. RELAXIN enhances differentiation and matrix mineralization through Relaxin/insulin-like family peptide receptor 2 (Rxfp2) in MC3T3-E1 cells in vitro. Bone 2014, 65 , 92-101. https://doi.org/10.1016/j.bone.2014.05.005
    54. Craig M. Smith, Berenice E. Chua, Cary Zhang, Andrew W. Walker, Mouna Haidar, David Hawkes, Fazel Shabanpoor, Mohammad Akhter Hossain, John D. Wade, K. Johan Rosengren, Andrew L. Gundlach. Central injection of relaxin-3 receptor (RXFP3) antagonist peptides reduces motivated food seeking and consumption in C57BL/6J mice. Behavioural Brain Research 2014, 268 , 117-126. https://doi.org/10.1016/j.bbr.2014.03.037
    55. P.J. Ryan, E.V. Krstew, M. Sarwar, A.L. Gundlach, A.J. Lawrence. Relaxin-3 mRNA levels in nucleus incertus correlate with alcohol and sucrose intake in rats. Drug and Alcohol Dependence 2014, 140 , 8-16. https://doi.org/10.1016/j.drugalcdep.2014.04.017
    56. M Kocan, M Sarwar, M A Hossain, J D Wade, R J Summers. Signalling profiles of H 3 relaxin, H 2 relaxin and R 3( BΔ 23–27) R / I 5 acting at the relaxin family peptide receptor 3 ( RXFP 3). British Journal of Pharmacology 2014, 171 (11) , 2827-2841. https://doi.org/10.1111/bph.12623
    57. José Ignacio Arroyo, Federico G. Hoffmann, Juan C. Opazo. Evolution of the Relaxin/Insulin-Like Gene Family in Anthropoid Primates. Genome Biology and Evolution 2014, 6 (3) , 491-499. https://doi.org/10.1093/gbe/evu023
    58. Fazel Shabanpoor, Ross A. D. Bathgate, John D. Wade, Mohammed Akhter Hossain, . C-Terminus of the B-Chain of Relaxin-3 Is Important for Receptor Activity. PLoS ONE 2013, 8 (12) , e82567. https://doi.org/10.1371/journal.pone.0082567
    59. Linda Jiaying Chan, Chrishan S. Samuel, Frances Separovic, Mohammed Akhter Hossain, John D. Wade. Relaxin and its role in fibrotic diseases. 2013, 60-78. https://doi.org/10.1039/9781849737081-00060
    60. Roy C.K. Kong, Emma J. Petrie, Biswaranjan Mohanty, Jason Ling, Jeremy C.Y. Lee, Paul R. Gooley, Ross A.D. Bathgate. The Relaxin Receptor (RXFP1) Utilizes Hydrophobic Moieties on a Signaling Surface of Its N-terminal Low Density Lipoprotein Class A Module to Mediate Receptor Activation. Journal of Biological Chemistry 2013, 288 (39) , 28138-28151. https://doi.org/10.1074/jbc.M113.499640
    61. D E Ganella, G E Callander, S Ma, C R Bye, A L Gundlach, R A D Bathgate. Modulation of feeding by chronic rAAV expression of a relaxin-3 peptide agonist in rat hypothalamus. Gene Therapy 2013, 20 (7) , 703-716. https://doi.org/10.1038/gt.2012.83
    62. Mohammed Akhter Hossain, Craig M. Smith, Philip J. Ryan, Elena Büchler, Ross A. D. Bathgate, Andrew L. Gundlach, John D. Wade. Chemical synthesis and orexigenic activity of rat/mouse relaxin-3. Amino Acids 2013, 44 (6) , 1529-1536. https://doi.org/10.1007/s00726-013-1478-0
    63. Philip J. Ryan, Elena Büchler, Fazel Shabanpoor, Mohammed Akhter Hossain, John D. Wade, Andrew J. Lawrence, Andrew L. Gundlach. Central relaxin-3 receptor (RXFP3) activation decreases anxiety- and depressive-like behaviours in the rat. Behavioural Brain Research 2013, 244 , 142-151. https://doi.org/10.1016/j.bbr.2013.01.034
    64. Leanne Satchell, Claire Glister, Emma C. Bleach, Richard G. Glencross, Andrew B. Bicknell, Yanzhenzi Dai, Ravinder Anand-Ivell, Richard Ivell, Philip G. Knight. Ovarian Expression of Insulin-Like Peptide 3 (INSL3) and Its Receptor (RXFP2) During Development of Bovine Antral Follicles and Corpora Lutea and Measurement of Circulating INSL3 Levels During Synchronized Estrous Cycles. Endocrinology 2013, 154 (5) , 1897-1906. https://doi.org/10.1210/en.2012-2232
    65. Anna Blasiak, Tomasz Blasiak, Marian H. Lewandowski, Mohammed Akhter Hossain, John D. Wade, Andrew L. Gundlach. Relaxin‐3 innervation of the intergeniculate leaflet of the rat thalamus – neuronal tract‐tracing and in vitro electrophysiological studies. European Journal of Neuroscience 2013, 37 (8) , 1284-1294. https://doi.org/10.1111/ejn.12155
    66. Fazel Shabanpoor, Mohammed Akhter Hossain, Feng Lin, John D. Wade. Sequential Formation of Regioselective Disulfide Bonds in Synthetic Peptides with Multiple Disulfide Bonds. 2013, 81-87. https://doi.org/10.1007/978-1-62703-544-6_5
    67. Andrew L. Gundlach, Craig M. Smith, Philip J. Ryan, Anna Blasiak, Francisco E. Olucha-Bordonau, Sherie Ma. Relaxins. 2013, 907-916. https://doi.org/10.1016/B978-0-12-385095-9.00121-4
    68. R. A. D. Bathgate, M. L. Halls, E. T. van der Westhuizen, G. E. Callander, M. Kocan, R. J. Summers. Relaxin Family Peptides and Their Receptors. Physiological Reviews 2013, 93 (1) , 405-480. https://doi.org/10.1152/physrev.00001.2012
    69. John D. Wade, Feng Lin, Mohammed Akhter Hossain, Raymond M. Dawson. Chemical synthesis and biological evaluation of an antimicrobial peptide gonococcal growth inhibitor. Amino Acids 2012, 43 (6) , 2279-2283. https://doi.org/10.1007/s00726-012-1305-z
    70. Linda J. Chan, K.Johan Rosengren, Sharon L. Layfield, Ross A.D. Bathgate, Frances Separovic, Chrishan S. Samuel, Mohammed A. Hossain, John D. Wade. Identification of Key Residues Essential for the Structural Fold and Receptor Selectivity within the A-chain of Human Gene-2 (H2) Relaxin. Journal of Biological Chemistry 2012, 287 (49) , 41152-41164. https://doi.org/10.1074/jbc.M112.409284
    71. Vinojini B. Nair, Chrishan S. Samuel, Frances Separovic, Mohammed Akhter Hossain, John D. Wade. Human relaxin-2: historical perspectives and role in cancer biology. Amino Acids 2012, 43 (3) , 1131-1140. https://doi.org/10.1007/s00726-012-1375-y
    72. Ana Cervera-Ferri, Yasamin Rahmani, Sergio Martínez-Bellver, Vicent Teruel-Martí, Joana Martínez-Ricós. Glutamatergic projection from the nucleus incertus to the septohippocampal system. Neuroscience Letters 2012, 517 (2) , 71-76. https://doi.org/10.1016/j.neulet.2012.04.014
    73. Mohammed Akhter Hossain, John D. Wade, Ross A.D. Bathgate. Chimeric relaxin peptides highlight the role of the A-chain in the function of H2 relaxin. Peptides 2012, 35 (1) , 102-106. https://doi.org/10.1016/j.peptides.2012.02.021
    74. Craig M. Smith, Philip J. Ryan, Ihaia T. Hosken, Sherie Ma, Andrew L. Gundlach. Relaxin-3 systems in the brain—The first 10 years. Journal of Chemical Neuroanatomy 2011, 42 (4) , 262-275. https://doi.org/10.1016/j.jchemneu.2011.05.013
    75. Mohammed Akhter Hossain, Laure Guilhaudis, Agnes Sonnevend, Samir Attoub, Bianca J. van Lierop, Andrea J. Robinson, John D. Wade, J. Michael Conlon. Synthesis, conformational analysis and biological properties of a dicarba derivative of the antimicrobial peptide, brevinin-1BYa. European Biophysics Journal 2011, 40 (4) , 555-564. https://doi.org/10.1007/s00249-011-0679-2
    76. H.A. van Duyvenvoorde, J. van Doorn, J. Koenig, L. Gauguin, W. Oostdijk, J.D. Wade, M. Karperien, C.A.L. Ruivenkamp, M. Losekoot, P.A. van Setten, M.J.E. Walenkamp, C. Noordam, P. De Meyts, J.M. Wit. The severe short stature in two siblings with a heterozygous IGF1 mutation is not caused by a dominant negative effect of the putative truncated protein. Growth Hormone & IGF Research 2011, 21 (1) , 44-50. https://doi.org/10.1016/j.ghir.2010.12.004
    77. Aldo Donizetti, Marcella Fiengo, Rosanna del Gaudio, Rossella Di Giaimo, Sergio Minucci, Francesco Aniello. Characterization and developmental expression pattern of the relaxin receptor rxfp1 gene in zebrafish. Development, Growth & Differentiation 2010, 52 (9) , 799-806. https://doi.org/10.1111/j.1440-169X.2010.01215.x
    78. B. M. C. McGowan, J. S. Minnion, K. G. Murphy, N. E. White, D. Roy, S. A. Stanley, W. S. Dhillo, J. V. Gardiner, M. A. Ghatei, S. R. Bloom. Central and peripheral administration of human relaxin‐2 to adult male rats inhibits food intake. Diabetes, Obesity and Metabolism 2010, 12 (12) , 1090-1096. https://doi.org/10.1111/j.1463-1326.2010.01302.x
    79. Xiao Luo, Ya-Li Liu, Sharon Layfield, Xiao-Xia Shao, Ross A.D. Bathgate, John D. Wade, Zhan-Yun Guo. A simple approach for the preparation of mature human relaxin-3. Peptides 2010, 31 (11) , 2083-2088. https://doi.org/10.1016/j.peptides.2010.07.022
    80. Seon-Yeong Kwak, Briony E. Forbes, Yoon-Sik Lee, Alessia Belgi, John D. Wade, Mohammed Akhter Hossain. Solid Phase Synthesis of an Analogue of Insulin, A0:R glargine, That Exhibits Decreased Mitogenic Activity. International Journal of Peptide Research and Therapeutics 2010, 16 (3) , 153-158. https://doi.org/10.1007/s10989-010-9218-8
    81. G. E. Callander, R. A. D. Bathgate. Relaxin family peptide systems and the central nervous system. Cellular and Molecular Life Sciences 2010, 67 (14) , 2327-2341. https://doi.org/10.1007/s00018-010-0304-z
    82. Mohammed Akhter Hossain, Chrishan S. Samuel, Claudia Binder, Tim D. Hewitson, Geoffrey W. Tregear, John D. Wade, Ross A. D. Bathgate. The chemically synthesized human relaxin-2 analog, B-R13/17K H2, is an RXFP1 antagonist. Amino Acids 2010, 39 (2) , 409-416. https://doi.org/10.1007/s00726-009-0454-1
    83. Hiroki Otsubo, Tatsushi Onaka, Hitoshi Suzuki, Akiko Katoh, Toyoaki Ohbuchi, Miwako Todoroki, Mizuki Kobayashi, Hiroaki Fujihara, Toru Yokoyama, Tetsuro Matsumoto, Yoichi Ueta. Centrally administered relaxin-3 induces Fos expression in the osmosensitive areas in rat brain and facilitates water intake. Peptides 2010, 31 (6) , 1124-1130. https://doi.org/10.1016/j.peptides.2010.02.020
    84. Emma T. van der Westhuizen, Arthur Christopoulos, Patrick M. Sexton, John D. Wade, Roger J. Summers. H2 Relaxin Is a Biased Ligand Relative to H3 Relaxin at the Relaxin Family Peptide Receptor 3 (RXFP3). Molecular Pharmacology 2010, 77 (5) , 759-772. https://doi.org/10.1124/mol.109.061432
    85. Pacharin Kamolkijkarn, Thitawan Prasertdee, Chawita Netirojjanakul, Pakornwit Sarnpitak, Somsak Ruchirawat, Songpon Deechongkit. Synthesis, biophysical, and biological studies of wild-type and mutant psalmopeotoxins—Anti-malarial cysteine knot peptides from Psalmopoeus cambridgei. Peptides 2010, 31 (4) , 533-540. https://doi.org/10.1016/j.peptides.2010.01.001
    86. Andrew L. Gundlach. Relaxin-3. 2010, 1-15. https://doi.org/10.1016/B978-008055232-3.63677-3
    87. Josh D. Silvertown, Anton Neschadim, Hsueh-Ning Liu, Patrick Shannon, Jagdeep S. Walia, Jessica C.H. Kao, Janice Robertson, Alastair J.S. Summerlee, Jeffrey A. Medin. Relaxin-3 and receptors in the human and rhesus brain and reproductive tissues. Regulatory Peptides 2010, 159 (1-3) , 44-53. https://doi.org/10.1016/j.regpep.2009.09.007
    88. Sherie Ma, Qian Sang, José L. Lanciego, Andrew L. Gundlach. Localization of relaxin‐3 in brain of Macaca fascicularis : Identification of a nucleus incertus in primate. Journal of Comparative Neurology 2009, 517 (6) , 856-872. https://doi.org/10.1002/cne.22197
    89. Thomas Hoeg‐Jensen. Design of Insulin Variants for Improved Treatment of Diabetes. 2009, 249-286. https://doi.org/10.1002/9780470749708.ch7
    90. John D. Wade, Feng Lin, M. Akhter Hossain, Fazel Shabanpoor, Suode Zhang, Geoffrey W. Tregear. The Chemical Synthesis of Relaxin and Related Peptides. Annals of the New York Academy of Sciences 2009, 1160 (1) , 11-15. https://doi.org/10.1111/j.1749-6632.2009.03951.x
    91. Brigham J. Hartley, Daniel J. Scott, Gabrielle E. Callander, Tracey N. Wilkinson, Despina E. Ganella, Chze K. Kong, Sharon Layfield, Tania Ferraro, Emma J. Petrie, Ross A. D. Bathgate. Resolving the Unconventional Mechanisms Underlying RXFP1 and RXFP2 Receptor Function. Annals of the New York Academy of Sciences 2009, 1160 (1) , 67-73. https://doi.org/10.1111/j.1749-6632.2009.03949.x
    92. Geoffrey W. Tregear, Ross A. D. Bathgate, Mohammed Akhter Hossain, Feng Lin, Suode Zhang, Fazel Shabanpoor, Daniel J. Scott, Sherie Ma, Andrew L. Gundlach, Chrishan S. Samuel, John D. Wade. Structure and Activity in the Relaxin Family of Peptides. Annals of the New York Academy of Sciences 2009, 1160 (1) , 5-10. https://doi.org/10.1111/j.1749-6632.2009.03955.x
    93. Andrew L. Gundlach, Sherie Ma, Qian Sang, Pei‐Juan Shen, Loretta Piccenna, Katayoun Sedaghat, Craig M. Smith, Ross A. D. Bathgate, Andrew J. Lawrence, Geoffrey W. Tregear, John D. Wade, David I. Finkelstein, Pascal Bonaventure, Changlu Liu, Timothy W. Lovenberg, Steve W. Sutton. Relaxin Family Peptides and Receptors in Mammalian Brain. Annals of the New York Academy of Sciences 2009, 1160 (1) , 226-235. https://doi.org/10.1111/j.1749-6632.2009.03956.x
    94. K. Johan Rosengren, Ross A. D. Bathgate, David J. Craik, Norelle L. Daly, Linda M. Haugaard‐Jönsson, Mohammed Akhter Hossain, John D. Wade. Structural Insights into the Function of Relaxins. Annals of the New York Academy of Sciences 2009, 1160 (1) , 20-26. https://doi.org/10.1111/j.1749-6632.2009.03833.x
    95. . Synthesis of Special Peptides and Peptide Conjugates. 2009, 365-409. https://doi.org/10.1002/9783527626038.ch6
    96. Chrishan S. Samuel, Simon G. Royce, Bin Chen, Huifang Cao, Jan A. Gossen, Geoffrey W. Tregear, Mimi L. K. Tang. Relaxin Family Peptide Receptor-1 Protects against Airway Fibrosis during Homeostasis But Not against Fibrosis Associated with Chronic Allergic Airways Disease. Endocrinology 2009, 150 (3) , 1495-1502. https://doi.org/10.1210/en.2008-1062
    97. Michelle Halls. Insulin-Like Peptide 3 (INSL3). 2009, 1-9. https://doi.org/10.1016/B978-008055232-3.64020-6
    98. Fazel Shabanpoor, Frances Separovic, John D. Wade. Chapter 1 The Human Insulin Superfamily of Polypeptide Hormones. 2009, 1-31. https://doi.org/10.1016/S0083-6729(08)00601-8
    99. Mohammed Akhter Hossain, K. Johan Rosengren, Suode Zhang, Ross A. D. Bathgate, Geoffrey W. Tregear, Bianca J. van Lierop, Andrea J. Robinson, John D. Wade. Solid phase synthesis and structural analysis of novel A-chain dicarba analogs of human relaxin-3 (INSL7) that exhibit full biological activity. Organic & Biomolecular Chemistry 2009, 7 (8) , 1547. https://doi.org/10.1039/b821882j
    100. John D. Wade. Double-stranded Cystine Peptides. 2008, 345-366. https://doi.org/10.1039/9781847559265-00345
    Load all citations
    Download PDF

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect