Journal article

1,3-Dichloroacetone: A Robust Reagent for Preparing Bicyclic Peptides

Qingqing Lin, Denham Hopper, Haoyue Zhang, Jordan Sfyris Qoon, Zihan Shen, John A Karas, Richard A Hughes, Susan E Northfield

ACS Omega | AMER CHEMICAL SOC | Published : 2020

Abstract

The chemical synthesis of cyclic peptides is a well-established area of research. This has been further expanded by development of bio-orthogonal reactions that enable access to peptides of greater structural complexity. One approach utilizes 1,3-dichloroacetone to selectively link free cysteine side-chains with an acetone-like bridge via an SN2 reaction. Here, we have used this reaction to dimerize cyclic peptide monomers to create novel bicyclic dimeric peptides. We investigated a range of reaction parameters to identify the optimal dimerization conditions for our model systems. One of the acetone-linked dimeric peptides was analyzed for proteolytic stability in human serum and was observe..

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Grants

Funding Acknowledgements

Project received funding from Multiple Sclerosis Research Australia, SN was supported by a Melbourne Neuroscience Institute fellowship. We thank Dr Dalia Ponce and the HRMS facility at the Department of Pharmacology and Therapeutics at the University of Melbourne for assistance in peptide characterization, Prof Philip Thompson and Dr Simon Mountford for NMR analysis on the DCA sample, and Prof Philip Thompson and A/Prof Akhter Hossain for proofreading.