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Chemistry A European J - 2024 - Wu - Total Chemical Synthesis of Aggregation‐Prone Disulfide‐Rich Starfish Peptides1.41 MB
Published VersionCC BY V4.0, Open Access
Journal article
Total Chemical Synthesis of Aggregation-Prone Disulfide-Rich Starfish Peptides
Chemistry: A European Journal, Vol.30(33), pp.1-10
2024
PMID: 38609334
Abstract
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. Our objective was to chemically synthesize Aso-RGP in its mature form, comprising two chains (A and B) and three disulfide bridges, omitting the C-peptide. Furthermore, we aimed to synthesize a newly identified relaxin-like peptide, Aso-RLP2, from COTS, which had not been previously synthesized. This paper report the first total chemical synthesis of Aso-RGP and Aso-RLP2. Aso-RGP synthesis proceeded without major issues, whereas the A-chain of Aso-RLP2, in its reduced and unfolded state with two free thiols, presented considerable challenges. These were initially marked by "messy" RP-HPLC profiles, typically indicative of synthesis failure. Surprisingly, oxidizing the A-chain significantly improved the RP-HPLC profile, revealing the main issue was not synthesis failure but the peptide's aggregation tendency, which initially obscured analysis. This discovery highlights the critical need to account for aggregation in peptide synthesis and analysis. Ultimately, our efforts led to the successful synthesis of both peptides with purities exceeding 95%.
Details
- Title
- Total Chemical Synthesis of Aggregation-Prone Disulfide-Rich Starfish Peptides
- Authors
- Hongkang Wu - Florey Institute of Neuroscience and Mental HealthPraveen Praveen - Florey Institute of Neuroscience and Mental HealthThomas Ng Handley - Florey Institute of Neuroscience and Mental HealthChaitra Chandrashekar - Florey Institute of Neuroscience and Mental HealthScott F Cummins - University of the Sunshine Coast, Queensland, Centre for BioinnovationRoss A D Bathgate - Florey Institute of Neuroscience and Mental HealthMohammed Akhter Hossain (Corresponding Author) - The University of Melbourne
- Publication details
- Chemistry: A European Journal, Vol.30(33), pp.1-10
- Publisher
- Wiley-VCH Verlag GmbH & Co. KGaA
- Date published
- 2024
- DOI
- 10.1002/chem.202400933
- ISSN
- 1521-3765; 0947-6539
- PMID
- 38609334
- Copyright note
- © 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Grants
- Organisation Unit
- School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 991022798402621
- Output Type
- Journal article
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