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Title: | AN INVESTIGATION OF RELAXIN-3 B-CHAIN STAPLED PEPTIDES AS NOVEL AGENTS FOR THE TREATMENT OF EATING AND NEUROPSYCHIATRIC DISORDERS | Authors: | SUBHI MARWARI | ORCID iD: | orcid.org/0000-0002-1447-8203 | Keywords: | Relaxin-3, RXFP3, Stapled peptide, Intranasal, Anxiety, Depression | Issue Date: | 18-Jan-2018 | Citation: | SUBHI MARWARI (2018-01-18). AN INVESTIGATION OF RELAXIN-3 B-CHAIN STAPLED PEPTIDES AS NOVEL AGENTS FOR THE TREATMENT OF EATING AND NEUROPSYCHIATRIC DISORDERS. ScholarBank@NUS Repository. | Abstract: | The neuropeptide relaxin-3 plays a crucial role in the normal function of the central nervous system and provides a blueprint for molecular mimicry that can drive drug discovery. However, the development of relaxin-3 peptide therapeutic has been limited with the challenges in synthesis and requirement of surgical implantation into the brain providing the limitation of therapeutic development of novel compounds. Introducing a “hydrocarbon-stapling” technology, we first rationally designed and tested a series of stapled peptides installed at the relaxin-3 B-chain sequence. Notably, the successful emergence of a lead stapled peptide demonstrated improved in-vitro and in-vivo pharmacological activity. Further, we aimed to validate the potential for non-invasive intranasal delivery of relaxin-3 and the lead stapled peptide in animal models. Our research findings have suggested that the strategy of intranasal delivery of “stapled” relaxin-3/RXFP3 system has a potential in pursuit of translational pharmacological approaches for eating and stress-related neuropsychiatric disorders. | URI: | http://scholarbank.nus.edu.sg/handle/10635/141742 |
Appears in Collections: | Ph.D Theses (Open) |
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