Biocompatible strategies for peptide macrocyclisation

Chemical Science, Год журнала: 2024, Номер 15(7), С. 2300 - 2322

Опубликована: Янв. 1, 2024

The identification of macrocyclic peptides in drug discovery demands not only advanced screening strategies but also robust and reliable synthetic methodologies to constrain under biocompatible conditions.

Язык: Английский

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Tryptophan-specific modification and diversification of peptides and proteins

Organic & Biomolecular Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

This review provides an account of the tryptophan-specific conjugation peptides and proteins its extensive application in imaging living cells, radiolabelling proteins, protein engineering, etc .

Язык: Английский

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Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion

Chemical Reviews, Год журнала: 2024, Номер 124(16), С. 9580 - 9608

Опубликована: Июль 2, 2024

Over 20 years ago, the pyrrolysine encoding translation system was discovered in specific archaea. Our Review provides an overview of how once obscure pyrrolysyl-tRNA synthetase (PylRS) tRNA pair, originally responsible for accurately translating enzymes crucial methanogenic metabolic pathways, laid foundation burgeoning field genetic code expansion. primary focus is discussion to successfully engineer PylRS recognize new substrates and exhibit higher

Язык: Английский

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Cysteine‐Specific Multifaceted Bioconjugation of Peptides and Proteins Using 5‐Substituted 1,2,3‐Triazines

Advanced Science, Год журнала: 2024, Номер 11(21)

Опубликована: Март 11, 2024

Abstract Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering drug discovery, of which cysteine‐specific modification strategies are prominent inherent nucleophilicity low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives achieve multifaceted bioconjugation targeting cysteine‐containing peptides proteins. On one hand, this represents an inaugural instance employing in biomolecular‐specific within physiological solution. other as powerful combination precision biorthogonality, strategy allows for one‐pot dual‐orthogonal functionalization biomolecules aldehyde group generated simultaneously. 1,2,3‐Triazine with diverse functional groups allow conjugation or proteins, while bi‐triazines enable peptide cyclization dimerization. The examination stability revealed potential reversible modification. This work establishes comprehensive platform identifying cysteine‐selective modifications, providing new avenues peptide‐based development, bioconjugation, chemical biology research.

Язык: Английский

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Selective Protein (Post-)modifications through Dynamic Covalent Chemistry: Self-activated S_NAr Reactions

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

SNAr reactions were remarkably accelerated using a pretargeting and activating unit based on dynamic covalent chemistry (DCvC). A Cys attack at the C–F bond aromatic ring of salicylaldehyde derivatives was only observed upon iminium formation with neighboring Lys residue model small peptides. Such self-activation ascribed to stronger electron-withdrawing capability respect that parent aldehyde stabilized transition state reaction, together higher preorganization reactive groups in cationic aldiminium species. This approach further applied for functionalization two antibodies. In both cases, presence group close proximity resulted noteworthy increase bioconjugation yields, excellent chemo-selectivity. Whereas modification an IgG1 antibody led stochastic product distributions, microenvironment selectivity noted when employing IgG4, line lower number residues hinge region latter. Additionally, postfunctionalization modified antibodies attained through exchange tethered derivative hydrazides, representing unprecedented "tag modify" selective strategy DCvC.

Язык: Английский

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Hard and soft electrons and holes

Chem, Год журнала: 2024, Номер 10(9), С. 2724 - 2744

Опубликована: Июль 8, 2024

The principle of hard and soft acids bases (HSAB) has given chemists a broad understanding the observed selectivity in variety reaction classes. As we become increasingly aware principle's serious limitations, this study provides an alternative approach. distinction between electrons holes (HSEH) adds to our reactivity. Because radicals are typically better stabilized at sites lone pairs sites, can easily distinguish them. Simple electron density differences (from three single-point functional theory [DFT] calculations) be used visualize effect condense into numerical descriptor. usefulness concept is demonstrated by reproducing experimentally reactivity wide range molecules, including larger examples relevant material pharmaceutical sciences.

Язык: Английский

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Peptide and Protein Cysteine Modification Enabled by Hydrosulfuration of Ynamide

ACS Central Science, Год журнала: 2024, Номер 10(9), С. 1742 - 1754

Опубликована: Авг. 21, 2024

Efficient functionalization of peptides and proteins has widespread applications in chemical biology drug discovery. However, the chemoselective site-selective modification remains a daunting task. Herein, highly efficient chemo-, regio-, stereoselective hydrosulfuration ynamide was identified as an method for precise by uniquely targeting thiol group cysteine (Cys) residues. This novel could be facilely operated aqueous buffer fully compatible with wide range proteins, including small model large full-length antibodies, without compromising their integrity functions. Importantly, this reaction provides Z-isomer corresponding conjugates exclusively superior stability, offering approach to peptide protein therapeutics. The potential application further exemplified Cys-bioconjugation variety ynamide-bearing functional molecules such molecule drugs, fluorescent/affinity tags, PEG polymers. It also proved redox proteomic analysis through Cys-alkenylation. Overall, study bioorthogonal tool Cys-specific functionalization, which will find broad synthesis peptide/protein conjugates.

Язык: Английский

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Advanced green synthesis: Solvent-free and catalyst-free reaction

Green Synthesis and Catalysis, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Allenamides as a Powerful Tool to Incorporate Diversity: Thia‐Michael Lipidation of Semisynthetic Peptides and Access to β‐Ketoamides

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Авг. 22, 2024

Abstract Lipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers more efficient late‐stage structural derivatisation peptide scaffold. It provides access to chemically diverse compounds possessing intriguing and non‐native moieties. Utilising allenamide, we report the first semisynthesis antimicrobial lipopeptides leveraging highly thia‐Michael addition lipophilic thiols. Using chemoenzymatically prepared polymyxin B nonapeptide (PMBN) as model scaffold, optimised allenamide‐mediated effected rapid near quantitative lipidation, affording vinyl sulfide‐linked lipopeptide derivatives. Harnessing utility this new methodology, 22 thiols unprecedented chemical diversity were introduced PMBN framework. These included alkyl thiols, substituted aromatic heterocyclic those bearing additional functional groups (e.g., amines), ultimately yielding analogues potent Gram‐negative activity substantially attenuated nephrotoxicity. Furthermore, facile routes transform allenamide into β ‐keto amide on unprotected peptides, offering powerful “jack‐of‐all‐trades” synthetic intermediate enable further modification.

Язык: Английский

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Synthesis and Characterization of Gold(I) N-Heterocyclic Carbenes Complexes Bearing Methacrylate Moiety

Journal of Organometallic Chemistry, Год журнала: 2025, Номер unknown, С. 123514 - 123514

Опубликована: Янв. 1, 2025

Язык: Английский

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