Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/138206
Title: CHARACTERISING AND DETERMINING THE SIGNALLING BIAS OF STAPLED PEPTIDE ANALOGUES OF THE RELAXIN-3 B CHAIN
Authors: JAYAKODY PATHIRANNEHELAGE THARINDUNEE JAYAKODY
Keywords: Relaxin-3, RXFP3, Signalling Bias, Stapled Peptides, Cell Signalling, GPCR
Issue Date: 31-May-2017
Source: JAYAKODY PATHIRANNEHELAGE THARINDUNEE JAYAKODY (2017-05-31). CHARACTERISING AND DETERMINING THE SIGNALLING BIAS OF STAPLED PEPTIDE ANALOGUES OF THE RELAXIN-3 B CHAIN. ScholarBank@NUS Repository.
Abstract: RXFP3, the cognate receptor of relaxin-3 is a GPCR. Structure activity relationship studies have revealed that relaxin-3 interacts and activates RXFP3 via the B chain which contains an alpha helix. Alpha helicity of small peptides such as the relaxin-3 B chain can be retained by hydrocarbon stapling. In this project, initially, two stapled peptide analogues of the relaxin-3 B chain are characterized by in silico modelling, binding studies, CD spectroscopy and signalling assays. Next, one of the peptides (14s18) is further analysed for stability in aqueous solutions and bias factors for signalling pathways are determined by the operational model of agonism. Compared to H3 Relaxin and Peptide 4 (13-17 staple), 14-18 stapled peptides are biased towards G-protein activation pathway over beta arrestin recruitment pathways. Thus, this study concludes that the position of the staple or stapling in general is a method of developing biased peptide ligands at RXFP3.
URI: http://scholarbank.nus.edu.sg/handle/10635/138206
Appears in Collections:Ph.D Theses (Open)

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