Tyrosine Conjugation Methods for Protein Labelling

Chemistry - A European Journal, Journal Year: 2020, Volume and Issue: 26(63), P. 14257 - 14269

Published: June 15, 2020

Abstract Over the last two decades, development of chemical biology and need for more defined protein conjugates have fostered active research on new bioconjugation techniques. In particular, a wide range biorthogonal labelling strategies been reported to functionalise phenol side chain tyrosines (Tyr). Tyr occur at medium frequency are partially buried surface, offering interesting opportunities site‐selective most reactive residues. Tyr‐targeting has proved effective designing important biomolecules including antibody–drug conjugates, fluorescent or radioactive probes, glycovaccines, aggregates, PEG conjugates. Innovative methods also site‐specific with ligand‐directed anchors specific affinity capture proteins. This review will present discuss these promising alternatives conventional nucleophilic lysine cysteine

Language: Английский

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Peptide Late-Stage Diversifications by Rhodium-Catalyzed Tryptophan C7 Amidation

Chem, Journal Year: 2020, Volume and Issue: 6(12), P. 3428 - 3439

Published: Nov. 20, 2020

Language: Английский

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Progress and perspectives on directing group-assisted palladium-catalysed C–H functionalisation of amino acids and peptides

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(16), P. 9278 - 9343

Published: Jan. 1, 2021

Peptide modifications can unlock a variety of compounds with structural diversity and abundant biological activity. In nature, peptide modifications, such as functionalisation at the side-chain position amino acids, are performed using post-translational modification enzymes or incorporation unnatural acids. However, accessing these remains challenge for organic chemists. During past decades, selective C-H activation/functionalisation has attracted considerable attention in synthetic chemistry pathway to modification. Various directing group strategies have been discovered that assist activation. particular, bidentate groups enable tuneable reversible coordination now recognised one most efficient methods site-selective activation numerous families compounds. Synthetic chemists harnessed β- γ-positions This method expanded an effective device late stage macrocyclisation total synthesis complex natural products. this review, we discuss various β-, γ-, δ-C(sp3)-H bond reactions acids formation C-X bonds aid their application late-stage

Language: Английский

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Late-stage stitching enabled by manganese-catalyzed C─H activation: Peptide ligation and access to cyclopeptides

Science Advances, Journal Year: 2021, Volume and Issue: 7(9)

Published: Feb. 26, 2021

Earth-abundant manganese catalyst enabled the expedient synthesis of cyclic peptides via activation inert C─H bonds.

Language: Английский

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Late‐stage C−H Functionalization of Tryptophan‐Containing Peptides with Thianthrenium Salts: Conjugation and Ligation

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(9)

Published: Dec. 30, 2022

Abstract Bioorthogonal late‐stage diversification of structurally complex peptides bears enormous potential for drug discovery and molecular imaging, among other applications. Herein, we report on a palladium‐catalyzed C−H arylation tryptophan‐containing with readily accessible modular arylthianthrenium salts. Under exceedingly mild reaction conditions, the was accomplished. The tunability ease preparation salts allowed expedient stitching drug, natural product, peptidic scaffolds by forging sterically congested biaryl linkages. robustness palladium catalysis regime reflected full tolerance plethora sensitive coordinating functional groups. Hence, our manifold enabled efficient access to highly decorated, labelled, conjugated, ligated linear cyclic peptides.

Language: Английский

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Diversification of pharmaceutical molecules via late-stage C(sp2)–H functionalization

Green Synthesis and Catalysis, Journal Year: 2023, Volume and Issue: 4(2), P. 104 - 123

Published: Jan. 2, 2023

C–H late-stage functionalization has gradually become a powerful approach for the rapid optimization of lead compounds' bioactivity. Significant advances in this field have been achieved past few years, mainly, system (hetero)aryl activation owing to importance moiety pharmaceutical. In review, we described selected recent examples how developed intermolecular C(sp2)–H methodologies involving diverse techniques diversify pharmaceutical molecules late stage.

Language: Английский

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Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 1030 - 1076

Published: Nov. 18, 2023

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new is start with old drug"

Language: Английский

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Therapeutic stapled peptides: Efficacy and molecular targets

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107137 - 107137

Published: March 23, 2024

Peptide stapling, by employing a stable, preformed alpha-helical conformation, results in the production of peptides with improved membrane permeability and enhanced proteolytic stability, compared to original peptides, provides an effective solution accelerate rapid development peptide drugs. Various reviews present stapling chemistries, anchoring residues one- or two-component cyclization, however, therapeutic stapled have not been systematically summarized, especially focusing on various disease-related targets. This review highlights latest advances drug facilitated application technology, including different techniques, synthetic accessibility, applicability biological targets, potential for solving problems, as well current status development. Stapled candidates classified analysed mainly receptor- ligand-based design against diseases, cancer, infectious inflammation, diabetes. is expected provide comprehensive reference rational diseases targets facilitate pharmacokinetic properties.

Language: Английский

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Manganese-Catalyzed Electrochemical Oxidation of Tryptophan-Containing Peptides and Indole Derivatives by O₂

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 3928 - 3939

Published: Feb. 20, 2025

Language: Английский

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MacrocyclizationviaC–H functionalization: a new paradigm in macrocycle synthesis

Organic & Biomolecular Chemistry, Journal Year: 2020, Volume and Issue: 18(10), P. 1851 - 1876

Published: Jan. 1, 2020

The growing emphasis on macrocycles in engaging difficult therapeutic targets such as protein-protein interactions and GPCRs via preferential adaptation of bioactive cell penetrating conformations has provided impetus to the search for de novo macrocyclization strategies that are efficient, chemically robust amenable diversity creation. An emerging paradigm based C-H activation logic, particular promise complex peptides, added a new dimension this pursuit, enabling efficacious access various sizes topologies with high atom step economy. Significant achievements methodologies their applications synthesis natural products drug-like molecules, employing strategic variations captured review. It is expected timely account will foster interest newer ways macrocycle construction among practitioners organic chemical biology advance field.

Language: Английский

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