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Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation (2024)
Journal Article
Smith, F. R., Meehan, D., Griffiths, R. C., Knowles, H. J., Zhang, P., Williams, H. E., …Mitchell, N. J. (2024). Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation. Chemical Science, 15(25), 9612-9619. https://doi.org/10.1039/d3sc05865d

Synthetic methods that enable the macrocyclisation of peptides facilitate the development of effective therapeutic and diagnostic tools. Herein we report a peptide cyclisation strategy based on intramolecular interception of visible-light-mediated cy... Read More about Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation.

Application of a Synthetic Ferredoxin‐Inspired [4Fe4S]‐Peptide Maquette as the Redox Partner for an [FeFe]‐Hydrogenase (2023)
Journal Article
Bombana, A., Shanmugam, M., Collison, D., Kibler, A. J., Newton, G. N., Jäger, C. M., …Mitchell, N. J. (2023). Application of a Synthetic Ferredoxin‐Inspired [4Fe4S]‐Peptide Maquette as the Redox Partner for an [FeFe]‐Hydrogenase. ChemBioChem, 24(18), Article e202300250. https://doi.org/10.1002/cbic.202300250

‘Bacterial-type’ ferredoxins host a cubane [4Fe4S]2+/+ cluster that enables these proteins to mediate electron transfer and facilitate a broad range of biological processes. Peptide maquettes based on the conserved cluster-forming motif have previous... Read More about Application of a Synthetic Ferredoxin‐Inspired [4Fe4S]‐Peptide Maquette as the Redox Partner for an [FeFe]‐Hydrogenase.

Diphosphoryl‐functionalized Polyoxometalates: Structurally and Electronically Tunable Hybrid Molecular Materials (2023)
Journal Article
Amin, S. S., Jones, K. D., Kibler, A. J., Damian, H. A., Cameron, J. M., Butler, K. S., …Newton, G. N. (2023). Diphosphoryl‐functionalized Polyoxometalates: Structurally and Electronically Tunable Hybrid Molecular Materials. Angewandte Chemie International Edition, 62(23), Article e202302446. https://doi.org/10.1002/anie.202302446

Herein, we report the synthesis and characterization of a new class of hybrid Wells–Dawson polyoxometalate (POM) containing a diphosphoryl group (P2O6X) of the general formula [P2W17O57(P2O6X)]6− (X=O, NH, or CR1R2). Modifying the bridging unit X was... Read More about Diphosphoryl‐functionalized Polyoxometalates: Structurally and Electronically Tunable Hybrid Molecular Materials.

Site‐Selective Installation of Nϵ ‐Modified Sidechains into Peptide and Protein Scaffolds via Visible‐Light‐Mediated Desulfurative C–C Bond Formation (2021)
Journal Article
Griffiths, R. C., Smith, F. R., Long, J. E., Scott, D., Williams, H. E. L., Oldham, N. J., …Mitchell, N. J. (2022). Site‐Selective Installation of Nϵ ‐Modified Sidechains into Peptide and Protein Scaffolds via Visible‐Light‐Mediated Desulfurative C–C Bond Formation. Angewandte Chemie, 134(2), Article e202110223. https://doi.org/10.1002/ange.202110223

Post-translational modifications (PTMs) enhance the repertoire of protein function and mediate or influence the activity of many cellular processes. The preparation of site-specifically and homogeneously modified proteins, to apply as tools to unders... Read More about Site‐Selective Installation of Nϵ ‐Modified Sidechains into Peptide and Protein Scaffolds via Visible‐Light‐Mediated Desulfurative C–C Bond Formation.

Mimicking native display of cd0873 on liposomes augments its potency as an oral vaccine against clostridioides difficile (2021)
Journal Article
Karyal, C., Palazi, P., Hughes, J., Griffiths, R. C., Persaud, R. R., Tighe, P. J., …Griffin, R. (2021). Mimicking native display of cd0873 on liposomes augments its potency as an oral vaccine against clostridioides difficile. Vaccines, 9(12), Article 1453. https://doi.org/10.3390/vaccines9121453

Mucosal vaccination aims to prevent infection mainly by inducing secretory IgA (sIgA) antibody, which neutralises pathogens and enterotoxins by blocking their attachment to epithelial cells. We previously demonstrated that encapsulated protein antige... Read More about Mimicking native display of cd0873 on liposomes augments its potency as an oral vaccine against clostridioides difficile.

Peptide Conjugation: The Chemical Synthesis of Site-Specifically Modified Proteins via Diselenide-Selenoester Ligation (2021)
Book Chapter
Griffiths, R. C., & Mitchell, N. J. (2021). Peptide Conjugation: The Chemical Synthesis of Site-Specifically Modified Proteins via Diselenide-Selenoester Ligation. In W. M. Hussein, R. J. Stephenson, & I. Toth (Eds.), Peptide Conjugation: Methods and Protocols (231-251). Humana Press. https://doi.org/10.1007/978-1-0716-1617-8

Peptide ligation techniques enable the controlled chemical synthesis of native and engineered proteins, including examples that display site-specific post-translational modifications (PTMs) and non-proteinogenic functionality. Diselenide-selenoester... Read More about Peptide Conjugation: The Chemical Synthesis of Site-Specifically Modified Proteins via Diselenide-Selenoester Ligation.

Site-Selective Modification of Peptides and Proteins via Interception of Free-Radical-Mediated Dechalcogenation (2020)
Journal Article
Griffiths, R. C., Smith, F. R., Long, J. E., Williams, H. E. L., Layfield, R., & Mitchell, N. J. (2020). Site-Selective Modification of Peptides and Proteins via Interception of Free-Radical-Mediated Dechalcogenation. Angewandte Chemie International Edition, 59(52), 23659-23667. https://doi.org/10.1002/anie.202006260

© 2020 The Authors. Published by Wiley-VCH GmbH The development of site-selective chemistry targeting the canonical amino acids enables the controlled installation of desired functionalities into native peptides and proteins. Such techniques facilita... Read More about Site-Selective Modification of Peptides and Proteins via Interception of Free-Radical-Mediated Dechalcogenation.

Accelerated protein synthesis via one–pot ligation–deselenization chemistry (2017)
Journal Article
Mitchell, N. J., Sayers, J., Kulkarni, S. S., Clayton, D., Goldys, A. M., Ripoll-Rozada, J., …Payne, R. J. (in press). Accelerated protein synthesis via one–pot ligation–deselenization chemistry. Chem, 2(5), https://doi.org/10.1016/j.chempr.2017.04.003

Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables t... Read More about Accelerated protein synthesis via one–pot ligation–deselenization chemistry.

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor (2017)
Journal Article
Weitsman, G., Mitchell, N. J., Evans, R., Cheung, A., Kalber, T. L., Bofinger, R., …Ng, T. (in press). Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor. Oncogene, https://doi.org/10.1038/onc.2016.522

Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the im... Read More about Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor.

One-pot ligation-oxidative deselenization at selenocysteine and selenocystine (2016)
Journal Article
Payne, R. J., Mitchell, N. J., Kulkarni, S. S., Wang, S., & Malins, L. (2017). One-pot ligation-oxidative deselenization at selenocysteine and selenocystine. Chemistry - A European Journal, 23(4), 946-952. https://doi.org/10.1002/chem.201604709

The use of native chemical ligation at selenocysteine (Sec) with peptide thioesters and additive-free selenocystine ligation with peptides bearing phenyl selenoesters, in concert with one-pot oxidative deselenization chemistry, is described. These ap... Read More about One-pot ligation-oxidative deselenization at selenocysteine and selenocystine.