Diversity-Oriented Peptide Stapling: A Third Generation Copper-Catalysed Azide-Alkyne Cycloaddition Stapling and Functionalisation Strategy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00475168" target="_blank" >RIV/61388963:_____/17:00475168 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1002/chem.201700128" target="_blank" >http://dx.doi.org/10.1002/chem.201700128</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/chem.201700128" target="_blank" >10.1002/chem.201700128</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Diversity-Oriented Peptide Stapling: A Third Generation Copper-Catalysed Azide-Alkyne Cycloaddition Stapling and Functionalisation Strategy

Popis výsledku v původním jazyce

The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling ( DOPS) methodology based on CuAAC chemistry. Stapling of peptides incorporating two azidemodified amino acids with 1,3,5-triethynylbenzene efficiently provides (i, i+7)- and ( i, i+9)- stapled peptides with a single free alkyne positioned on the staple, which can be further conjugated or dimerised. A unique feature of the present method is that it provides easy access to radiolabelled stapled peptides by catalytic tritiation of the alkyne positioned on the staple.

Název v anglickém jazyce

Diversity-Oriented Peptide Stapling: A Third Generation Copper-Catalysed Azide-Alkyne Cycloaddition Stapling and Functionalisation Strategy

Popis výsledku anglicky

The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling ( DOPS) methodology based on CuAAC chemistry. Stapling of peptides incorporating two azidemodified amino acids with 1,3,5-triethynylbenzene efficiently provides (i, i+7)- and ( i, i+9)- stapled peptides with a single free alkyne positioned on the staple, which can be further conjugated or dimerised. A unique feature of the present method is that it provides easy access to radiolabelled stapled peptides by catalytic tritiation of the alkyne positioned on the staple.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Chemistry - A European Journal

ISSN

0947-6539

e-ISSN

—

Svazek periodika

23

Číslo periodika v rámci svazku

14

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

6

Strana od-do

3490-3495

Kód UT WoS článku

000395775700032

EID výsledku v databázi Scopus

2-s2.0-85013249260