Publications by authors named "T P B Handley"

Article Synopsis
  • Insulin-like peptide 5 (INSL5) primarily targets the RXFP4 receptor found in the colorectum and has potential for treating gastrointestinal issues like constipation.
  • While INSL5 can bind to the RXFP3 receptor, it does not activate it, highlighting the specificity of the INSL5/RXFP4 pathway for therapeutic applications.
  • The study developed an engineered INSL5 analogue (A13:B7-24-GG) that features a simpler structure, resulting in easier synthesis and improved potency and selectivity compared to native INSL5, making it a strong candidate for constipation treatment.
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The control of malaria, a disease caused by parasites that kills over half a million people every year, is threatened by the continual emergence and spread of drug resistance. Therefore, new molecules with different mechanisms of action are needed in the antimalarial drug development pipeline. Peptides developed from host defense molecules are gaining traction as anti-infectives due to theood of inducing drug resistance.

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Human insulin-like peptide 5 (INSL5) is a gut hormone produced by colonic L-cells, and its biological functions are mediated by Relaxin Family Peptide Receptor 4 (RXFP4). Our preliminary data indicated that RXFP4 agonists are potential drug leads for the treatment of constipation. More recently, we designed and developed a novel RXFP4 antagonist, A13-nR that was shown to block agonist-induced activity in cells and animal models.

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Article Synopsis
  • INSL5 and relaxin-3 are peptides that play key roles in gut and brain functions, targeting class A GPCRs RXFP4 and RXFP3, which may help treat colon and neurological disorders, respectively.
  • The study focuses on developing a tracking system using NanoBiT complementation for better binding assays of RXFP3 and RXFP4, allowing for efficient quantification without complex separation processes.
  • Researchers created a specific agonist (SmBiT-R3/I5) for RXFP3/4, demonstrating its binding affinity in cell lines and optimizing membrane assays for effective high-throughput ligand analysis.
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A relaxin-like gonad-stimulating peptide (RGP), Aso-RGP, featuring six cysteine residues, was identified in the Crown-of-Thorns Starfish (COTS, Acanthaster cf. solaris) and initially produced through recombinant yeast expression. This method yielded a single-chain peptide with an uncleaved C-peptide (His Tag) and suboptimal purity.

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