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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Phosphine-promoted Thiol-Specific Bioconjugation with Allylic Acetates

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Thiol-specific modification of proteins through conjugation with small molecules represents a critical advancement in biological research and therapeutic development, particularly the context antibody-drug conjugates (ADCs) for targeted cancer therapy. Despite widespread use maleimide-based linkers, their stability under physiological conditions remains major limitation, often compromising efficacy. In this investigation, we developed novel efficient thiol-specific bioconjugation strategy that employs allylic acetate, activated by recyclable solid phosphine catalyst. This approach achieves high yields demonstrates robust bio-compatible, room-temperature conditions. Notably, it sets new record fastest cysteine-conjugation reaction rate reported to date, constant k₂ = 1.49 × 10⁶ M^{− 1}s^{− 1}. The method expands substrate scope introduces sustainable, environmentally friendly ADC linker design, offering significant creation stable, biocompatible, therapeutically effective compounds.

Язык: Английский

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Dynamic Fluorescence Sensing of Bromide Ions by Photochromic Bi(III)‐Coordination Polymers Based on a Ligand Integrated by Naphthalene Diimides and Pyridinium in Solution and Films

Small, Год журнала: 2023, Номер 20(16)

Опубликована: Ноя. 30, 2023

Bismuth(III)-based complexes have garnered increasing attention in fluorescence sensing due to their environmentally friendly and sustainable characteristics. A Bismuth(III) coordination polymer (CP),1-Cl based on a naphthalene diimides(NDI)-pyridinium is synthesized by an situ reaction method. Notable for its sensitivity visible light, 1-Cl shows excellent photochromic properties, the integration of NDI pyridinium one ligand makes photogenerated radicals more stable. Structural analysis theoretical calculations are employed investigate potential pathway photoinduced electron transfer (ET) during process. Notably, aqueous solutions, displays extraordinary enhancement response bromide ion (Br

Язык: Английский

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NSPs: chromogenic linkers for fast, selective, and irreversible cysteine modification

Chemical Science, Год журнала: 2024, Номер 15(28), С. 10997 - 11004

Опубликована: Янв. 1, 2024

o -Nitrostyryl-pyridinium ions (NSPs) are easily accessible electrophiles that react rapidly and irreversibly with sulfhydryl groups accompanied by a large bathochromic shift.

Язык: Английский

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