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dc.contributor.authorLee, HS
dc.contributor.authorWang, SH
dc.contributor.authorDaniel, JT
dc.contributor.authorHossain, MA
dc.contributor.authorClark, RJ
dc.contributor.authorBathgate, RAD
dc.contributor.authorRosengren, KJ
dc.date.accessioned2020-11-17T04:11:28Z
dc.date.available2020-11-17T04:11:28Z
dc.date.issued2020-10-01
dc.identifierpii: biomedicines8100415
dc.identifier.citationLee, H. S., Wang, S. H., Daniel, J. T., Hossain, M. A., Clark, R. J., Bathgate, R. A. D. & Rosengren, K. J. (2020). Exploring the Use of Helicogenic Amino Acids for Optimising Single Chain Relaxin-3 Peptide Agonists. BIOMEDICINES, 8 (10), https://doi.org/10.3390/biomedicines8100415.
dc.identifier.issn2227-9059
dc.identifier.urihttp://hdl.handle.net/11343/251728
dc.description.abstractRelaxin-3 is a highly conserved two-chain neuropeptide that acts through its endogenous receptor the Relaxin Family Peptide-3 (RXFP3) receptor. The ligand/receptor system is known to modulate several physiological processes, with changes in food intake and anxiety-levels the most well studied in rodent models. Agonist and antagonist analogues based on the native two-chain peptide are costly to synthesise and not ideal drug leads. Since RXFP3 interacting residues are found in the relaxin B-chain only, this has been the focus of analogue development. The B-chain is unstructured without the A-chain support, but in single-chain variants structure can be induced by dicarba-based helical stapling strategies. Here we investigated whether alternative helical inducing strategies also can enhance structure and activity at RXFP3. Combinations of the helix inducing α-aminoisobutyric acid (Aib) were incorporated into the sequence of the relaxin-3 B-chain. Aib residues at positions 13, 17 and 18 partially reintroduce helicity and activity of the relaxin-3 B-chain, but other positions are generally not suited for modifications. We identify Thr21 as a putative new receptor contact residue important for RXFP3 binding. Cysteine residues were also incorporated into the sequence and cross-linked with dichloroacetone or α, α'-dibromo-m-xylene. However, in contrast to previously reported dicarba variants, neither were found to promote structure and RXFP3 activity.
dc.languageEnglish
dc.publisherMDPI
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleExploring the Use of Helicogenic Amino Acids for Optimising Single Chain Relaxin-3 Peptide Agonists
dc.typeJournal Article
dc.identifier.doi10.3390/biomedicines8100415
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.source.titleBiomedicines
melbourne.source.volume8
melbourne.source.issue10
melbourne.source.pages1-16
dc.rights.licenseCC BY
melbourne.elementsid1469383
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602263
melbourne.contributor.authorBathgate, Ross
melbourne.contributor.authorHossain, Mohammed
dc.identifier.eissn2227-9059
melbourne.accessrightsOpen Access


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