Intramolecular methionine alkylation constructs sulfonium tethered peptides for protein conjugation

Yang, Lixue; Lian, Chenshan; Hou, Zhanjun; Wang, Dongyuan; Wang, Rui; Wan, Chuan; Zhong, Wanjin; Zhao, Rongtong; Wang, Yuena; Li, Shuiming; Yin, Feng; Li, Zigang

doi:10.1039/d0cc00377h

Cited by 15 publications

(10 citation statements)

References 28 publications

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“…Reaction with PDZ-RGS3 in PBS buffer at pH 7.4 showed site-selective conjugation of the peptides to Cys33 and Cys34, whereas a third Cys residue, Cys73, displayed low reactivity. 103 The method was also used to develop a covalent peptide inhibitor against BFL-1, a protein belonging to the anti-apoptotic B cell lymphoma 2 (Bcl-2) protein family and containing three free Cys residues, conjugating selectively to Cys55. The peptide did not conjugate to other Cys-containing proteins like PDZ, Bcl-2, MgrA, and sortase A.…”

Section: Cysteine (Cys)mentioning

confidence: 99%

Chemical modification of proteins – challenges and trends at the start of the 2020s

2023

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Section: Cysteine (Cys)mentioning

confidence: 99%

Chemical modification of proteins – challenges and trends at the start of the 2020s

2023

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“…Following the Met-Cys initializing peptide stapling, 133 Li and co-workers obtained another sulfonium tethered stapled peptides via aliphatic halide mediated intramolecular cyclization. 254 A halogenated aliphatic acid was first incorporated into the N-terminus of Met-contained linear peptide, which subsequently underwent a spontaneous cleavage from resin and Met alkylation (Scheme 46). A series of aliphatic halides were investigated for cyclization efficiency, among which 3bromopropanoic acid provided the highest yield (92%).…”

Section: N-terminus-met Via Chemo-selective Alkylationmentioning

confidence: 99%

“…Thus the sulfonium stapled peptides could be used for site-specific and proximity-promoted protein labeling, forming the peptide−protein conjugate (Scheme 46). 254…”

Section: N-terminus-met Via Chemo-selective Alkylationmentioning

confidence: 99%

Stapled Helical Peptides Bearing Different Anchoring Residues

et al. 2020

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A large proportion of protein–protein interactions (PPIs) occur between a short peptide and a globular protein domain; the peptides involved in surface interactions play important roles, and there is great promise for using peptide motifs to interfere with protein interactions. Peptide inhibitors show more promise in blocking large surface protein interactions compared to small molecule inhibitors. However, peptides have drawbacks including poor stability against circulating proteolytic enzymes and an intrinsic inability to penetrate cell membranes. Stapled helical peptides, by adopting a preformed, stable α-helical conformation, exhibit improved proteolytic stability and membrane permeability compared to linear bioactive peptides. In this review, we summarize the broad aspects of peptide stapling for chemistry, biophysics, and biological applications and specifically highlight the methodology by providing an inventory of different anchoring residues categorized into two natural amino acids, two nonnatural amino acids, or a combination of natural and nonnatural amino acids. Additional advantages of specific peptide stapling techniques, including but not limited to reversibility, bio-orthogonal reactivity, and photoisomerization, are also discussed individually. This review is expected to provide a broad reference for the rational design of druggable stapled peptides targeting therapeutic proteins, particularly those involved in PPIs, by considering the impact of anchoring residues, functional cross-linkers, physical staple length, staple components, and the staple motif on the biophysical properties of the peptides.

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“…For example, Li et al produced sulfonium-tethered cyclic peptides via intramolecular alkylation. 39 Cationic peptides have cell binding abilities and can function either as cell penetrating peptides or as antimicrobial peptides. 40 However, this cationic charge is not always favorable for many potential bioconjugate and biomaterials applications, as it can disrupt cellular membranes.…”

Section: Modification Of Thioether Groupsmentioning

confidence: 99%

Peptide and protein engineering by modification of backbone and sidechain functional groups

Kordbacheh

Kasko

2021

Polymer International

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Modifications of the sidechain and backbone of peptides and proteins are commonly used to improve their stability, to enhance their biological function, to enable and improve imaging and detection capabilities via conjugation to imaging agents and to otherwise introduce new properties. The most common approaches for modification and conjugation typically target amino acids such as lysine and cysteine. However, less abundant residues such as tyrosine, methionine and tryptophan are also potential targets for orthogonal modification. Non-traditional modifications of common amino acids such as cysteine can also be used to introduce novel functional groups in a peptide sidechain. Additionally, modification via sortase is also very precise and site specific in biological conditions. This mini-review article describes recent advances in selective modification reactions of peptides and proteins via these less common approaches.

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Intramolecular methionine alkylation constructs sulfonium tethered peptides for protein conjugation

Abstract: Continuous efforts have been invested in the selective modification of proteins.

Cited by 15 publications

References 28 publications

Chemical modification of proteins – challenges and trends at the start of the 2020s

Chemical modification of proteins – challenges and trends at the start of the 2020s

Stapled Helical Peptides Bearing Different Anchoring Residues

Peptide and protein engineering by modification of backbone and sidechain functional groups

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