Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late-Stage Functionalisation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F23%3A73620842" target="_blank" >RIV/61989592:15310/23:73620842 - isvavai.cz</a>

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202307782" target="_blank" >https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202307782</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.202307782" target="_blank" >10.1002/anie.202307782</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late-Stage Functionalisation

Popis výsledku v původním jazyce

Peptide stapling is a robust strategy for generating enzymatically stable, macrocyclic peptides. The incorporation of biologically relevant tags(such as cell-penetrating motifs or fluorescent dyes) into peptides, while preserving their binding interactions and enhancing their stability, is highly sought after. Consequently, the quest for novel peptide stapling methodologies that would easily incorporate such motifs, remains eminent. Despite the unique opportunities offered by tryptophan’s indole scaffold for targeted functionalisation, its utilisation in peptide stapling waslimited comparedto other amino acids. Herein, we present an unprecedentedapproach for peptide stapling using the tryptophan-mediated Petasis reaction(TMPR). This method represents a versatile tool for the synthesis of both stapled and labelled peptides, applicable to both solution and solid-phase synthesis. Importantly, the utilisation of the Petasis reaction in combinationwith tryptophan represents a significant advancementin the field of peptide stapling, facilitating the formation of stapled peptides in one straightforward, multicomponent fashion, while circumventing formation of undesired by-products –a persistent challenge in current methodologies. Furthermore, this approach allows forefficient and diverse late-stage peptide modifications, thereby enablingrapid production of numerous conjugates for biological and medicinal applications.

Název v anglickém jazyce

Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late-Stage Functionalisation

Popis výsledku anglicky

Peptide stapling is a robust strategy for generating enzymatically stable, macrocyclic peptides. The incorporation of biologically relevant tags(such as cell-penetrating motifs or fluorescent dyes) into peptides, while preserving their binding interactions and enhancing their stability, is highly sought after. Consequently, the quest for novel peptide stapling methodologies that would easily incorporate such motifs, remains eminent. Despite the unique opportunities offered by tryptophan’s indole scaffold for targeted functionalisation, its utilisation in peptide stapling waslimited comparedto other amino acids. Herein, we present an unprecedentedapproach for peptide stapling using the tryptophan-mediated Petasis reaction(TMPR). This method represents a versatile tool for the synthesis of both stapled and labelled peptides, applicable to both solution and solid-phase synthesis. Importantly, the utilisation of the Petasis reaction in combinationwith tryptophan represents a significant advancementin the field of peptide stapling, facilitating the formation of stapled peptides in one straightforward, multicomponent fashion, while circumventing formation of undesired by-products –a persistent challenge in current methodologies. Furthermore, this approach allows forefficient and diverse late-stage peptide modifications, thereby enablingrapid production of numerous conjugates for biological and medicinal applications.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GN22-07138O" target="_blank" >GN22-07138O: Konformačně zamčené konjugáty peptidů a léčiv jako platforma pro cílená terapeutika</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

ISSN

1433-7851

e-ISSN

1521-3773

Svazek periodika

62

Číslo periodika v rámci svazku

34

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

9

Strana od-do

"e202307782-1"-"e202307782-9"

Kód UT WoS článku

001027654300001

EID výsledku v databázi Scopus

2-s2.0-85164694874