Cys-Lys stapling for unprotected peptides via tunable linkers.

Kaizhen Miao, Bei Fu, Leiyang Bai, Chengliang Li, Xuefeng Jiang

Abstract read

In one paragraph

Article in National science review, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

A CThe New phytologist · 2026
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Kaizhen MiaoHainan Institute of East China Normal University, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Petroleum Molecular & Process Engineering, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

Bei FuHainan Institute of East China Normal University, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Petroleum Molecular & Process Engineering, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

Leiyang BaiHainan Institute of East China Normal University, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Petroleum Molecular & Process Engineering, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

Chengliang LiHainan Institute of East China Normal University, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Petroleum Molecular & Process Engineering, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

Xuefeng JiangHainan Institute of East China Normal University, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Petroleum Molecular & Process Engineering, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.ORCID https://orcid.org/0000-0002-1849-6572

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Stapling has emerged as a transformative paradigm in peptide chemistry, enabling precise conformational control to endow peptides with augmented biophysical properties, including enhanced proteolytic stability and target-binding affinity. Although symmetric macrocyclization strategies have been investigated, non-symmetric stapling of native peptide scaffolds remains underexplored, owing to intricate synthetic challenges associated with achieving concurrent chemoselectivity and site selectivity. This limitation primarily stems from the requirement for orthogonal reactivity in modifying distinct proteinogenic residues while preserving native side-chain functionalities under biocompatible conditions. Herein, a non-symmetric stapling is disclosed for cysteine-lysine (Cys-Lys) crosslinking in unprotected peptides and proteins via unsymmetrically tunable linkers with high chemoselectivity and regioselectivity in a self-assembly manner, in which a library of 17 stapling reagents with adjustable length, angle, flexibility, rigidity and lipophilicity was comprehensively established for relay Cys-Lys ligation, facilitating the macrocyclization of intervening loops (6-30 amino acids) into 25-40-membered rings under physiologically compatible conditions. The conformationally restricted peptide displayed strengthened

Indexed as

chemoselectivitycyclic peptidesCys–Lys staplingsite selectivitytunable linkersunprotected peptides

Identifiers

PMID41216488

DOI10.1093/nsr/nwaf406

PMCPMC12596731

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.