Robotic synthesis of peptides containing metal-oxide-based amino acids

She, S., Bell, N. L. , Zheng, D., Mathieson, J. S., Castro, M. D., Long, D.-L. , Koehnke, J. and Cronin, L. (2022) Robotic synthesis of peptides containing metal-oxide-based amino acids. Chem, 8(10), pp. 2734-2748. (doi: 10.1016/j.chempr.2022.07.007)

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Abstract

Peptides display a range of important properties, controlled by the intrinsic nature of organic side chains, regarding redox activity, charge density, and structure. Here, we demonstrate a new synthetic approach to insert non-coded amino acids that contain metal oxide groups into a desired peptide sequence with a commercial peptide synthesizer. This approach allowed us to design and isolate a range of highly anionic peptides with various sequences, including the amyloid Aβ17–20, the amphiphilic KFE8, and a bacterial chaperone DnaK substrate. By taking advantage of both the inorganic polyoxometalate-based motif and the peptide sequence, the resultant POM peptides enable significant inhibition of amyloid aggregation, switch a β sheet into a β turn, and enhance binding with the molecular chaperone DnaK. Therefore, we show it is possible to program the robotic synthesis of peptides with functional inorganic amino acids as a generic approach for the design and exploration of next-generation artificial biological-inorganic structures.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Zheng, Mr Dazhong and Long, Dr Deliang and Mathieson, Dr Jennifer and Koehnke, Professor Jesko and She, Dr Shan and Castro Spencer, Mrs Maria Diana and Bell, Dr Nicola and Cronin, Professor Lee
Authors: She, S., Bell, N. L., Zheng, D., Mathieson, J. S., Castro, M. D., Long, D.-L., Koehnke, J., and Cronin, L.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Chem
Publisher:Elsevier (Cell Press)
ISSN:2451-9308
ISSN (Online):2451-9294
Published Online:08 August 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Chem 8(10): 2734-2748
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
166449Programmable Molecular Metal Oxides (PMMOs) - From Fundamentals to ApplicationLeroy CroninEngineering and Physical Sciences Research Council (EPSRC)EP/J015156/1Chemistry
190796Programmable 'Digital' Synthesis for Discovery and Scale-up of Molecules, Clusters and NanomaterialsLeroy CroninEngineering and Physical Sciences Research Council (EPSRC)EP/L023652/1Chemistry
166779Innovative Manufacturing Research Centre for Continuous Manufacturing and Crystallisation (CMAC)Leroy CroninEngineering and Physical Sciences Research Council (EPSRC)EP/I033459/1Chemistry
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167864Energy and the Physical Sciences: Hydrogen Production using a Proton Electron BufferLeroy CroninEngineering and Physical Sciences Research Council (EPSRC)EP/K023004/1Chemistry
190796Programmable 'Digital' Synthesis for Discovery and Scale-up of Molecules, Clusters and NanomaterialsLeroy CroninEngineering and Physical Sciences Research Council (EPSRC)EP/L023652/1Chemistry
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301905PPOM-PTTLeroy CroninEuropean Commission (EC)798821Chemistry
310456Exploitation of enzyme promiscuity to generate ribosomal natural product diversityJesko KoehnkeEuropean Commission (EC)101002326Chemistry