Biospecific Chemistry for Covalent Linking of Biomacromolecules

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(13), P. 8516 - 8549

Published: June 24, 2024

Interactions among biomacromolecules, predominantly noncovalent, underpin biological processes. However, recent advancements in biospecific chemistry have enabled the creation of specific covalent bonds between biomolecules, both vitro and vivo. This Review traces evolution proteins, emphasizing role genetically encoded latent bioreactive amino acids. These acids react selectively with adjacent natural groups through proximity-enabled bioreactivity, enabling targeted linkages. We explore various designed to target different protein residues, ribonucleic acids, carbohydrates. then discuss how these novel linkages can drive challenging properties capture transient protein-protein protein-RNA interactions Additionally, we examine application peptides as potential therapeutic agents site-specific conjugates for native antibodies, highlighting their capacity form stable molecules. A significant focus is placed on reactive therapeutics (PERx), a pioneering technology therapeutics. detail its wide-ranging applications immunotherapy, viral neutralization, radionuclide therapy. Finally, present perspective existing challenges within avenues future exploration advancement this rapidly evolving field.

Language: Английский

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Click Chemistry for Biofunctional Polymers: From Observing to Steering Cell Behavior

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Click chemistry has become one of the most powerful construction tools in field organic chemistry, materials science, and polymer as it offers hassle-free platforms for high-yielding synthesis novel easy functionalization strategies. The absence harsh reaction conditions or complicated workup procedures allowed rapid development biofunctional polymeric materials, such biopolymers, tailor-made surfaces, stimulus-responsive polymers, etc. In this review, we discuss various types click reactions─including azide-alkyne cycloadditions, nucleophilic radical thiol reactions, a range cycloadditions (Diels-Alder, tetrazole, nitrile oxide, etc.), sulfur fluoride exchange (SuFEx) reaction, oxime-hydrazone reactions─and their use formation study polymers. Following that, state-of-the-art biological applications "click"-biofunctionalized including both passive (e.g., biosensing bioimaging) "active" ones that aim to direct changes biosystems, e.g., drug delivery, antiviral action, tissue engineering. conclusion, have outlined future directions existing challenges click-based polymers medicinal clinical applications.

Language: Английский

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Intramolecular Friedel–Crafts Reactions of Sulfamoyl Fluorides, Fluorosulfates, and Sulfuramidimidoyl Fluorides

Organic Letters, Journal Year: 2025, Volume and Issue: 27(6), P. 1356 - 1361

Published: Jan. 30, 2025

Sultams are valuable heterocycles with numerous applications, particularly as pharmacophores. Previous syntheses of these compounds usually require metal-catalyzed cyclization or multiple-step processes. Here, we report a straightforward strategy for accessing important motifs by developing the intramolecular Friedel-Crafts sulfamoyl fluorides under mild conditions. Our protocol also accommodates fluorosulfates and sulfuramidimidoyl fluorides, which rarely utilized in reactions.

Language: Английский

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Base-Free SuFEx Reaction Promoted by Silica Gel for the Synthesis of β-Sultams

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

β-Sultams are recognized as potential antibacterial agents and crucial building blocks in chemical synthesis. Herein, a "SuFEx on silica gel" approach has been developed for one-step synthesis of β-sultams utilizing readily available amines ethenesulfonyl fluoride (ESF). This process involves sequential Michael addition to ESF, followed by an intramolecular SuFEx reaction promoted gel. Silica gel facilitates the activation sulfonyl through hydrogen bonding between SVI-F surface hydroxyl groups eliminates HF formed during reaction. Notably, use base, which is typically required nearly all known reactions, was rendered unnecessary. The β-sultam moiety successfully incorporated into 26 tested primary amines, including pharmaceuticals natural products, high yields, showcasing broad applications this method.

Language: Английский

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Click processes orthogonal to CuAAC and SuFEx forge selectively modifiable fluorescent linkers

Nature Chemistry, Journal Year: 2023, Volume and Issue: 16(3), P. 426 - 436

Published: Dec. 13, 2023

Language: Английский

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Radical Hydro-Fluorosulfonylation of Propargylic Alcohols via Electron Donor–Acceptor Photoactivation

Organic Letters, Journal Year: 2024, Volume and Issue: 26(7), P. 1410 - 1415

Published: Feb. 15, 2024

A radical hydro-fluorosulfonylation of propargyl alcohols with FSO2Cl is presented based on the photoactivation electron donor–acceptor (EDA) complex. The reaction avoids requirement for photocatalysts, bases, hydrogen donor reagents, any other additives, and harsh conditions, enabling facile synthesis various functionalized γ-hydroxy (E)-alkenylsulfonyl fluorides. These multifunctional sulfonyl fluorides can be further diversified, providing access to privileged molecules biological relevance.

Language: Английский

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Modular synthesis of functional libraries by accelerated SuFEx click chemistry

Chemical Science, Journal Year: 2024, Volume and Issue: 15(11), P. 3879 - 3892

Published: Jan. 1, 2024

The Accelerated SuFEx Click Chemistry (ASCC) protocol, adapted to a 96-well plate format, has been applied the late-stage derivatization of bioactive molecules and array synthesis anticancer agents, showcasing its potential for drug discovery.

Language: Английский

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Enantiospecific Synthesis of Aniline-Derived Sulfonimidamides

Organic Letters, Journal Year: 2023, Volume and Issue: 25(30), P. 5666 - 5670

Published: July 25, 2023

Reaction of sulfonimidoyl fluorides with anilines and Ca(NTf2)2 results in the formation chiral sulfonimidamides. The reaction proceeds inversion stereocenter at a sulfur atom. Enantiospecificity was observed for all studied non-heterocyclic anilines. Combined experimental computational mechanistic studies highlight chelate-type coordination group to SN2-like transition state, which leaving F– coordinates Ca2+ ion.

Language: Английский

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Machine learning-accelerated discovery of heat-resistant polysulfates for electrostatic energy storage

Nature Energy, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Language: Английский

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N-Fluorosulfonyl Guanidine: An Entry to N-Guanyl Sulfamides and Sulfamates

Organic Letters, Journal Year: 2024, Volume and Issue: 26(15), P. 3202 - 3207

Published: April 5, 2024

Here, we present the straightforward synthesis of N-fluorosulfonyl guanidine (1) from two industrial feedstocks, hydrochloride and sulfuryl fluoride (SO2F2), using SuFEx chemistry. Compound 1 exhibits excellent stability under ambient conditions displays unique reactivity toward amines phenols to generate N-guanyl sulfamides sulfamates that have rarely been accessed. Notably, water serves as an effective solvent in this process. Our protocol provides a reliable pathway for investigation these novel guanidine-containing molecules.

Language: Английский

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