Chromophore Optimization in Organometallic Au(III) Cys Arylation of Peptides and Proteins for 266 nm Photoactivation DOI Creative Commons

Jacob W. Silzel,

Cheng‐Wei Chen,

Colomba M. Sanchez‐Marsetti

и другие.

Analytical Chemistry, Год журнала: 2024, Номер 96(36), С. 14581 - 14589

Опубликована: Авг. 28, 2024

Cysteine is the most reactive naturally occurring amino acid due to presence of a free thiol, presenting tantalizing handle for covalent modification peptides/proteins. Although many mass spectrometry experiments could benefit from site-specific Cys, utility direct arylation has not been thoroughly explored. Recently, Spokoyny and co-workers reported Au(III) organometallic reagent that robustly arylates Cys tolerates wide variety solvents conditions. Given chromophoric nature aryl groups known susceptibility carbon–sulfur bonds photodissociation, we set out identify an group efficiently cleave at 266 nm. A streamlined workflow was developed facilitate rapid examination large number aryls with minimal sample using simple test peptide, RAAACGVLK. We were able several yield abundant homolytic photodissociation adjacent short activation times (<10 ms). In addition, characterized radical products created by subjecting product ions further collisional activation. Finally, tested human hemoglobin, identified reaction conditions efficient intact proteins, evaluated photochemistry these ions.

Язык: Английский

In Silico Screening of P,N-Ligands Facilitates Optimization of Au(III)-Mediated S-Arylation DOI Creative Commons
Joseph W. Treacy, James A. R. Tilden, Elaine Y. Chao

и другие.

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

In silico examination of 13 P , N -ligated Au( iii ) OACs determined the key mechanistic factors governing )-mediated S -arylation. Three complexes were synthesized which exhibited bimolecular coordination rate constants as high 20 200 M −1 s .

Язык: Английский

Процитировано

2
Exploring the Electronic and Steric Effects of Hemilabile (P^N) Ligands in Redox Gold Catalysis: Application to the Cross-Coupling Reaction of Aliphatic Amines with Aryl Iodides DOI

Urvashi Urvashi,

Saurabh Rai, Gaurav Shukla

и другие.

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

Herein, we report 17 new (P^N) ligands for redox gold catalysis, featuring various substituents at -C4, -C5, and -C6 of the aryl ring nitrogen handle. Rate kinetics experiments revealed that electron-rich -C4 -C5 positions enhanced rate oxidative addition Au(I) with C(sp2)-Br bonds compared to electron-poor substituents. Further, an unprecedented gold-catalyzed arylation aliphatic amines using electronically rich ligand (L6) -OMe group position.

Язык: Английский

Процитировано

1
Organometallic Oxidative Addition Complexes for S-Arylation of Free Cysteines DOI
Hayden R. Montgomery, Alexander M. Spokoyny, Heather D. Maynard

и другие.

Bioconjugate Chemistry, Год журнала: 2024, Номер 35(7), С. 883 - 889

Опубликована: Июнь 24, 2024

Development of bioconjugation strategies to efficiently modify biomolecules is key importance for fundamental and translational scientific studies. Cysteine

Язык: Английский

Процитировано

5
Electronic Effects of Bidentate P,N-Ligands on the Elementary Steps of Au(I)/Au(III) Reactions Relevant to Cross-Coupling Chemistry DOI Creative Commons
Joseph W. Treacy, Elaine Y. Chao, Grace E. Kunkel

и другие.

Organic Letters, Год журнала: 2024, Номер unknown

Опубликована: Дек. 9, 2024

Oxidant-free Au(I)/Au(III)-catalyzed cross-coupling has been recently enabled by the use of bidentate

Язык: Английский

Процитировано

5
A Versatile Method for Site-Specific Chemical Installation of Aromatic Posttranslational Modification Analogs into Proteins DOI Creative Commons

Xiaoxi Lin,

Shaswati Mandal, Raj V. Nithun

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(37), С. 25788 - 25798

Опубликована: Сен. 3, 2024

Posttranslational modifications (PTMs) of proteins play central roles in regulating the protein structure, interactome, and functions. A notable modification site is aromatic side chain Tyr, which undergoes such as phosphorylation nitration. Despite biological physiological importance Tyr-PTMs, our current understanding mechanisms by these contribute to human health disease remains incomplete. This knowledge gap arises from absence natural amino acids that can mimic PTMs lack synthetic tools for site-specific introduction into proteins. Herein, we describe a facile method chemical installation through palladium-mediated S-C(sp

Язык: Английский

Процитировано

4
Phosphine-promoted Thiol-Specific Bioconjugation with Allylic Acetates DOI Creative Commons
Teck‐Peng Loh, Xiaohong Li, Tao Xu

и другие.

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

Опубликована: Март 24, 2025

Abstract 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− 1s− 1. The method expands substrate scope introduces sustainable, environmentally friendly ADC linker design, offering significant creation stable, biocompatible, therapeutically effective compounds.

Язык: Английский

Процитировано

0
Gold-Catalyzed Deallylative C–S Cross-Coupling Reactions DOI

Prafulla Bera,

Tanmayee Nanda,

Nivrutti B. Barhate

и другие.

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Herein, we report the gold-catalyzed deallylative C-S cross-coupling reaction through ligand-enabled Au(I)/Au(III) redox catalysis. One of major challenges in reactions is to prevent catalyst deactivation caused by formation a strong gold-sulfur bond. We discovered that use allyl phenyl sulfide as sulfur surrogate facilitates dynamic equilibrium between cationic Au(I) and Au(I)-sulfide complexes, overcoming gold quenching problem. A detailed mechanistic investigation, including 31P NMR studies, mass analysis, stoichiometric experiments, provided valuable insights into mechanism, which further supported computational studies.

Язык: Английский

Процитировано

0
Gold-Catalyzed Cross-Coupling Reactions of Organoiodides with Disulfides: Access to Aryl Sulfides and Vinyl Sulfide Derivatives DOI

Lizhu Zhang,

Yan-Fei Hu, Fen Zhao

и другие.

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Thioethers and their derivatives play important roles in synthetic chemistry, medicinal materials science. Herein, we report a hemilabile P,N-ligand-assisted gold-catalyzed C-S cross-coupling reaction of organoiodides with disulfides. In this reaction, alkyl or aryl disulfides react smoothly vinyl iodides to afford series sulfide good excellent yields. The robust capabilities thioether synthesis are exemplified by the readily available easily handled reagents as well compatibility wide range functional groups.

Язык: Английский

Процитировано

0
A systematic kinetic assay of phenylsulfonyl pyridine derivatives with free thiol for site-specific modification of proteins DOI

Xing Zhang,

Mohan Li,

Ben‐Guang Chen

и другие.

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

Опубликована: Янв. 1, 2025

This study examined the kinetics of phenylsulfonyl pyridines to free thiol, with reactivity that can be tuned by an order magnitude 1–5. The pyridine derivatives provide a powerful tool for precise protein modifications under mild conditions.

Язык: Английский

Процитировано

0
Comparison of Cyclic and Linear PEG Conjugates DOI Creative Commons
Grace E. Kunkel, Qingyang Zhou, Joseph W. Treacy

и другие.

Bioconjugate Chemistry, Год журнала: 2024, Номер 35(6), С. 744 - 749

Опубликована: Май 29, 2024

Bioconjugation of polymers to proteins is a method impart improved stability and pharmacokinetic properties biologic systems. However, the precise effects polymer architecture on resulting bioconjugates are not well understood. Particularly, cyclic known possess unique features such as decreased hydrodynamic radius when compared their linear counterparts same molecular weight, but have yet been studied. Here, we report first bioconjugation polymer, poly(ethylene glycol) (PEG), model protein, T4 lysozyme, containing single engineered cysteine residue (V131C). We compare activity this conjugate with those PEG-T4 lysozyme analogue similar weight. Furthermore, used dynamics (MD) simulations determine behavior polymer–protein conjugates in solution. introduce potential candidates for improvement therapeutics.

Язык: Английский

Процитировано

2