94
THE FLOREY INSTITUTE OF NEUROSCIENCE & MENTAL HEALTH ANNUAL REPORT 2012
Roy Kong •
Poster; Relaxin 2012: 6th International Conference on Relaxin and Related Peptides; Florence, Italy, October 2012
•
Poster; 7th International meeting on the Molecular Pharmacology of G Protein-Coupled Receptors, Melbourne, Australia, December 6th - 8th, 2012
led to the development of a novel relaxin analogue which is selective for its own receptor and which has no cross reactivity for the receptor, RXFP2, of a related peptide INSL3.
Editorial positions John Wade
Neuropeptides
95
publications 1.
Bathgate RA, Zhang S, Hughes RA, Rosengren KJ and Wade JD, The structural determinants of insulin-like Peptide 3 activity, Front Endocrinol (Lausanne), 3:11,2012, PMID: 22654853
2.
Callander GE, Ma S, Ganella DE, Wimmer VC, Gundlach AL, Thomas WG and Bathgate RA, Silencing relaxin-3 in nucleus incertus of adult rodents: a viral vector-based approach to investigate neuropeptide function, PLoS One, 7:e42300,2012, PMID: 22876314
•
3.
Poster; 38th Lorne Conference on Protein Structure and Function, Lorne, Australia, 5th-9th Feb 2012
Editor in Chief, International Journal of Peptide Research & Therapeutics 2005-
Chan LJ, Rosengren KJ, Layfield SL, Bathgate RA, Separovic F, Samuel CS, Hossain MA and Wade JD, Identification of key residues essential for the structural fold and receptor selectivity within the A-chain of H2 relaxin, J Biol Chem, 2012, PMID: 23024363
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Editor in Chief, Biochemical Compounds 2012-
4.
•
Poster; Melbourne Protein Group student symposium, 5th July 2012
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Editor, Journal of Peptide Science, 1999-
Chow BS, Chew EG, Zhao C, Bathgate RA, Hewitson TD and Samuel CS, Relaxin Signals through a RXFP1-pERK-nNOS-NO-cGMP-Dependent Pathway to UpRegulate Matrix Metalloproteinases: The Additional Involvement of iNOS, PLoS One, 7:e42714,2012, PMID: 22936987
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Editor, Protein & Peptide Letters, 2002-
5.
•
Poster; 7th International meeting on the Molecular Pharmacology of G Protein-Coupled Receptors, Melbourne, Australia, December 6th - 8th, 2012
Ganella DE, Callander GE, Ma S, Bye CR, Gundlach AL and Bathgate RA, Modulation of feeding by chronic rAAV expression of a relaxin-3 peptide agonist in rat hypothalamus, Gene Ther, 2012, PMID: 23135160
6.
Ganella DE, Ryan PJ, Bathgate RA and Gundlach AL, Increased feeding and body weight gain in rats after acute and chronic activation of RXFP3 by relaxin-3 and receptor-selective peptides: functional and therapeutic implications, Behav Pharmacol, 23:516-25,2012, PMID: 22854307
7.
Gundlach AL, Ryan PJ. , Galanin, The Handbook of Biologically Active Peptides [Internet]. San Diego: Elsevier, 766-75, 2012,
8.
Gundlach AL, Smith CM, Ryan PJ, Blasiak A, Olucha-Bordonau FE, Ma S., Relaxins, The Handbook of Biologically Active Peptides [Internet]. San Diego, USA: Elsevier, 2012,
9.
Hossain MA, Wade JD and Bathgate RA, Chimeric relaxin peptides highlight the role of the A-chain in the function of H2 relaxin, Peptides, 35:102-6,2012, PMID: 22414484
10.
Nair VB, Samuel CS, Separovic F, Hossain MA and Wade JD, Human relaxin-2: historical perspectives and role in cancer biology, Amino Acids, 2012, PMID: 22855207
Natalie Witteveen •
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Editor, Amino Acids, 2008-
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Editorial Board Member, Chemical Biology & Drug Design, 2006-
Maria Oh
•
Poster; 7th International meeting on the Molecular Pharmacology of G Protein-Coupled Receptors, Melbourne, Australia, December 6th - 8th, 2012
Editorial Board Member, International Journal of Peptides, 2006-
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Editorial Board Member, Frontiers in EndocrinologyMolecular and Structural Endocrinology, 2010-
Peptide and Protein Chemistry
{{Conferences
We employ modern chemical peptide synthesis methods together with structure-based drug design and development to produce novel peptidomimetics with improved receptor selectivity, potency and pharmacokinetics. Our primary research focus is on complex insulin-like peptides including the ovarian peptide, relaxin, and the neuropeptide, relaxin-3.
11.
2. 12th International Chinese Peptide Symposium, Shenyang, China (2012)
Olucha-Bordonau FE, Otero-Garcia M, Sanchez-Perez AM, Nunez A, Ma S and Gundlach AL, Distribution and targets of the relaxin-3 innervation of the septal area in the rat, J Comp Neurol, 520:1903-39,2012, PMID: 22134882
12.
3. 7th British Peptide & Protein Symposium, Cambridge, UK (2012)
Scott DJ and Pluckthun A, Direct Molecular Evolution of Detergent-Stable G Protein-Coupled Receptors using Polymer Encapsulated Cells, J Mol Biol, 2012, PMID: 23164568
13.
Scott DJ, Rosengren KJ and Bathgate RA, The Different Ligand-Binding Modes of Relaxin Family Peptide Receptors RXFP1 and RXFP2, Mol Endocrinol, 2012, PMID: 22973049
14.
Shabanpoor F, Akhter Hossain M, Ryan PJ, Belgi A, Layfield S, Kocan M, Zhang S, Samuel CS, Gundlach AL, Bathgate RA, Separovic F and Wade JD, Minimization of human relaxin-3 leading to high-affinity analogues with increased selectivity for relaxin-family peptide 3 receptor (RXFP3) over RXFP1, Journal of Medicinal Chemistry, 55:1671-81,2012, PMID: 22257012
15.
Shabanpoor F, Bathgate RA, Belgi A, Chan LJ, Nair VB, Wade JD and Hossain MA, Site-specific conjugation of a lanthanide chelator and its effects on the chemical synthesis and receptor binding affinity of human relaxin-2 hormone, Biochem Biophys Res Commun, 420:253-6,2012, PMID: 22425984
16.
Wade JD, Lin F, Hossain MA and Dawson RM, Chemical synthesis and biological evaluation of an antimicrobial peptide gonococcal growth inhibitor, Amino Acids, 2012, PMID: 22555649
17.
Zhang WJ, Luo X, Liu YL, Shao XX, Wade JD, Bathgate RA and Guo ZY, Site-specific DOTA/europium-labeling of recombinant human relaxin-3 for receptorligand interaction studies, Amino Acids, 43:983-92,2012, PMID: 22187146
``Research highlights for 2012 Our laboratory has continued to make significant progress in the identification of the key structural features of the insulinlike peptides, relaxin and relaxin-3, that are responsible for the binding and activation of their respective primary G-protein coupled receptors, RXFP1 and 3. Both peptides possess an insulin-like structure in which two peptides chains are linked together by three disulfide bonds. Relaxin is principally an ovarian hormone that has a number of physiological roles, one of which is to regulate the level of collagen throughout the body. Relaxin-3 possesses a similar overall structure but is a neuropeptide that is expressed by the brain and which appears to have a critical role in regulating mood and stress systems. Because of their similar global structures, relaxin-3 can cross react with the receptor for relaxin; this can potentially complicate our attempts to better understand the role of relaxin-3 in the brain because the relaxin receptor is also present in this organ.
1.
1st International Bachem Peptide Symposium, Basel, Switzerland (2012)
4. 32 European Peptide Symposium, Athens, Greece (2012) 5. Relaxin & Related Peptides 2012 Symposium, Florence, Italy (2012)
However, by using chemical peptide synthesis, selective amino acid mutation together with sequential truncation was undertaken on each of the two chains that make up each of relaxin-3 to produce novel mimetics. These were shown to possess relaxin-3 receptor selectivity while retaining nearnative potency. Importantly, these new analogues are much simpler structurally and therefore easier to make which will greatly facilitate the neurobiological studies that are being undertaken by our colleagues in the laboratory of Andrew Gundlach. Such studies will determine whether these analogues possess clinical potential for treating psychiatric disorders such as anxiety and depression. Parallel chemical methods have also
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