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)

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 Mathieson, Dr Jennifer and Long, Dr Deliang and She, Dr Shan and Koehnke, Professor Jesko and Bell, Dr Nicola and Castro Spencer, Mrs Maria Diana 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
166449		Programmable Molecular Metal Oxides (PMMOs) - From Fundamentals to Application	Leroy Cronin	Engineering and Physical Sciences Research Council (EPSRC)	EP/J015156/1	Chemistry
190796		Programmable 'Digital' Synthesis for Discovery and Scale-up of Molecules, Clusters and Nanomaterials	Leroy Cronin	Engineering and Physical Sciences Research Council (EPSRC)	EP/L023652/1	Chemistry
166779		Innovative Manufacturing Research Centre for Continuous Manufacturing and Crystallisation (CMAC)	Leroy Cronin	Engineering and Physical Sciences Research Council (EPSRC)	EP/I033459/1	Chemistry
166449		Programmable Molecular Metal Oxides (PMMOs) - From Fundamentals to Application	Leroy Cronin	Engineering and Physical Sciences Research Council (EPSRC)	EP/J015156/1	Chemistry
167864		Energy and the Physical Sciences: Hydrogen Production using a Proton Electron Buffer	Leroy Cronin	Engineering and Physical Sciences Research Council (EPSRC)	EP/K023004/1	Chemistry
190796		Programmable 'Digital' Synthesis for Discovery and Scale-up of Molecules, Clusters and Nanomaterials	Leroy Cronin	Engineering and Physical Sciences Research Council (EPSRC)	EP/L023652/1	Chemistry
172151		SMARTPOM: Artificial-Intelligence Driven Discovery and Synthesis of Polyoxometalate Clusters	Leroy Cronin	European Research Council (ERC)	670467	Chemistry
301905		PPOM-PTT	Leroy Cronin	European Commission (EC)	798821	Chemistry
310456		Exploitation of enzyme promiscuity to generate ribosomal natural product diversity	Jesko Koehnke	European Commission (EC)	101002326	Chemistry