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Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan (2023)
Journal Article
Lee, J. C., Cuthbertson, J. D., & Mitchell, N. J. (2023). Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan. Organic Letters, 25(29), 5459-5464. https://doi.org/10.1021/acs.orglett.3c01795

Across eukaryotic proteomes, tryptophan is the least abundant of the 20 canonical amino acids, which makes it an ideal chemical handle for the late-stage functionalization of peptide and protein scaffolds with minimal production of undesired isoforms... Read More about Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan.

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.

Cysteine-Selective Modification of Peptides and Proteins via Desulfurative C−C Bond Formation (2023)
Journal Article
Griffiths, R. C., Smith, F. R., Li, D., Wyatt, J., Rogers, D. M., Long, J. E., …Mitchell, N. (2023). Cysteine-Selective Modification of Peptides and Proteins via Desulfurative C−C Bond Formation. Chemistry - A European Journal, 29(16), Article e202202503. https://doi.org/10.1002/chem.202202503

The site-selective modification of peptides and proteins facilitates the preparation of targeted therapeutic agents and tools to interrogate biochemical pathways. Among the numerous bioconjugation techniques developed to install groups of interest, t... Read More about Cysteine-Selective Modification of Peptides and Proteins via Desulfurative C−C Bond Formation.

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., 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 International Edition, 61(2), Article e202110223. https://doi.org/10.1002/anie.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.

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, 132(52), 23867-23875. https://doi.org/10.1002/ange.202006260

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 facilitate the development of polypeptide conjugates to... Read More about Site‐Selective Modification of Peptides and Proteins via Interception of Free‐Radical‐Mediated Dechalcogenation.

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.

Development of lipopolyplexes for gene delivery: a comparison of the effects of differing modes of targeting peptide display on the structure and transfection activities of lipopolyplexes (2018)
Journal Article
Bofinger, R., Zaw-Thin, M., Mitchell, N. J., Patrick, P. S., Stowe, C., Gomez-Ramirez, A., …Tabor, A. B. (2018). Development of lipopolyplexes for gene delivery: a comparison of the effects of differing modes of targeting peptide display on the structure and transfection activities of lipopolyplexes. Journal of Peptide Science, e3131. https://doi.org/10.1002/psc.3131

The design, synthesis and formulation of non‐viral gene delivery vectors is an area of renewed research interest. Amongst the most efficient non‐viral gene delivery systems are lipopolyplexes, in which cationic peptides are co‐formulated with plasmid... Read More about Development of lipopolyplexes for gene delivery: a comparison of the effects of differing modes of targeting peptide display on the structure and transfection activities of lipopolyplexes.

Construction of challenging proline–proline junctions via diselenide–selenoester ligation chemistry (2018)
Journal Article
Sayers, J., Karpati, P. M. T., Mitchell, N. J., Goldys, A. M., Kwong, S. M., Firth, N., …Payne, R. J. (2018). Construction of challenging proline–proline junctions via diselenide–selenoester ligation chemistry. Journal of the American Chemical Society, 140(41), 13327-13334. https://doi.org/10.1021/jacs.8b07877

Polyproline sequences are highly abundant in prokaryotic 10 and eukaryotic proteins, where they serve as key components of 11 secondary structure. To date, construction of the proline?proline motif 12 has not been possible owing to steric congestion... Read More about Construction of challenging proline–proline junctions via diselenide–selenoester ligation chemistry.

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 ?-selenoaspartate and ?-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.

Single addition of an allyl amine monomer enables access to end-functionalized RAFT polymers via native chemical ligation (2016)
Journal Article
Isahak, N., Gody, G., Malins, L. R., Mitchell, N. J., Payne, R. J., & Perrier, S. (in press). Single addition of an allyl amine monomer enables access to end-functionalized RAFT polymers via native chemical ligation. Chemical Communications, 52, https://doi.org/10.1039/C6CC06010B

A novel method for the introduction of a single protected amine-functional monomer at the chain end of RAFT polymers has been developed. This monomer addition, in concert with native chemical ligation, facilitated the development of a simple and vers... Read More about Single addition of an allyl amine monomer enables access to end-functionalized RAFT polymers via native chemical ligation.

PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells (2016)
Journal Article
Rogers, S., Fey, D., McCloy, R. A., Parker, B. L., Mitchell, N. J., Payne, R. J., …Burgess, A. (2016). PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells. Journal of Cell Science, 129(7), 1340-1354. https://doi.org/10.1242/jcs.179754

Entry into mitosis is driven by the phosphorylation of thousands of substrates, under the master control of Cdk1. During entry into mitosis, Cdk1, in collaboration with MASTL kinase, represses the activity of the major mitotic protein phosphatases, P... Read More about PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells.

Rapid additive-free selenocystine-selenoester peptide ligation (2015)
Journal Article
Mitchell, N., Malins, L. R., Liu, X., Thompson, R. E., Chan, B., Radom, L., & Payne, R. J. (2015). Rapid additive-free selenocystine-selenoester peptide ligation. Journal of the American Chemical Society, 137(44), 14011-14014. doi:10.1021/jacs.5b07237

Peptide ligation chemistry at selenol amino acids (2013)
Journal Article
Malins, L. R., Mitchell, N. J., & Payne, R. J. (2014). Peptide ligation chemistry at selenol amino acids. Journal of Peptide Science, 20(2), 64-77. https://doi.org/10.1002/psc.2581

The convergent assembly of peptide fragments by native chemical ligation has revolutionized the way in which proteins can be accessed by chemical synthesis. A variation of native chemical ligation involves the reaction of peptides bearing an N‐termin... Read More about Peptide ligation chemistry at selenol amino acids.