Transition metal catalyzed site-selective cysteine diversification of proteins
Name
10.1515_pac-2020-0504.pdf
Description
Published version
Size
3.58 MB
Format
Adobe PDF
Checksum (MD5)
310d76d9668b65930293921ad7aaec4a
Author(s)
Jbara, Muhammad
Date Issued
July 13, 2020
Journal
Pure and Applied Chemistry
Publisher
Walter de Gruyter GmbH
Citation
Jbara, Muhammad. "Transition metal catalyzed site-selective cysteine diversification of proteins" Pure and Applied Chemistry, vol. 93, no. 2, 2021, pp. 169-186.
Version
Final published version
Abstract
Site-specific protein conjugation is a critical step in the generation of unique protein analogs for a range of basic research and therapeutic developments. Protein transformations must target a precise residue in the presence of a plethora of functional groups to obtain a well-characterized homogeneous product. Competing reactive residues on natural proteins render rapid and selective conjugation a challenging task. Organometallic reagents have recently emerged as a powerful strategy to achieve site-specific labeling of a diverse set of biopolymers, due to advances in water-soluble ligand design, high reaction rate, and selectivity. The thiophilic nature of various transition metals, especially soft metals, makes cysteine an ideal target for these reagents. The distinctive reactivity and selectivity of organometallic-based reactions, along with the unique reactivity and abundancy of cysteine within the human proteome, provide a powerful platform to modify native proteins in aqueous media. These reactions often provide the modified proteins with a stable linkage made from irreversible cross-coupling steps. Additionally, transition metal reagents have recently been applied for the decaging of cysteine residues in the context of chemical protein synthesis. Orthogonal cysteine protecting groups and functional tags are often necessary for the synthesis of challenging proteins, and organometallic reagents are powerful tools for selective, rapid, and water-compatible removal of those moieties. This review examines transition metal-based reactions of cysteine residues for the synthesis and modification of natural peptides and proteins.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1515/pac-2020-0504
