Diversity-oriented peptide stapling: a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy

Thu Phuong Tran; Christian Ørnbøl Larsen; Tobias Røndbjerg; Martina de Foresta; Micha Ben Achim Kunze; Ales Marek; Jacob Hartvig Løper; Lotte-Emilie Boyhus; Astrid Knuhtsen; Kresten Lindorff-Larsen; Daniel Sejer Pedersen

doi:10.1002/chem.201700128

Diversity-oriented peptide stapling: a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy

Thu Phuong Tran, Christian Ørnbøl Larsen, Tobias Røndbjerg, Martina de Foresta, Micha Ben Achim Kunze, Ales Marek, Jacob Hartvig Løper, Lotte-Emilie Boyhus, Astrid Knuhtsen, Kresten Lindorff-Larsen, Daniel Sejer Pedersen

Biomolecular Sciences

17 Citationer (Scopus)

Abstract

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 azide-modified 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.

Originalsprog	Engelsk
Tidsskrift	Chemistry: A European Journal
Vol/bind	23
Udgave nummer	14
Sider (fra-til)	3490-3495
Antal sider	6
ISSN	0947-6539
DOI	https://doi.org/10.1002/chem.201700128
Status	Udgivet - 8 mar. 2017

Adgang til dokumentet

10.1002/chem.201700128

Citationsformater

Tran, T. P., Larsen, C. Ø., Røndbjerg, T., de Foresta, M., Kunze, M. B. A., Marek, A., Hartvig Løper, J., Boyhus, L-E., Knuhtsen, A., Lindorff-Larsen, K., & Pedersen, D. S. (2017). Diversity-oriented peptide stapling: a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy. Chemistry: A European Journal, 23(14), 3490-3495. https://doi.org/10.1002/chem.201700128

Diversity-oriented peptide stapling : a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy. / Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias et al.

I: Chemistry: A European Journal, Bind 23, Nr. 14, 08.03.2017, s. 3490-3495.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Tran, TP, Larsen, CØ, Røndbjerg, T, de Foresta, M, Kunze, MBA, Marek, A, Hartvig Løper, J, Boyhus, L-E, Knuhtsen, A, Lindorff-Larsen, K & Pedersen, DS 2017, 'Diversity-oriented peptide stapling: a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy', Chemistry: A European Journal, bind 23, nr. 14, s. 3490-3495. https://doi.org/10.1002/chem.201700128

@article{36ccf9aa4a2c44bc9eb4386feba4f833,

title = "Diversity-oriented peptide stapling: a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy",

abstract = "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 azide-modified 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.",

author = "Tran, {Thu Phuong} and Larsen, {Christian {\O}rnb{\o}l} and Tobias R{\o}ndbjerg and {de Foresta}, Martina and Kunze, {Micha Ben Achim} and Ales Marek and {Hartvig L{\o}per}, Jacob and Lotte-Emilie Boyhus and Astrid Knuhtsen and Kresten Lindorff-Larsen and Pedersen, {Daniel Sejer}",

note = "{\textcopyright} 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2017",

month = mar,

day = "8",

doi = "10.1002/chem.201700128",

language = "English",

volume = "23",

pages = "3490--3495",

journal = "Chemistry: A European Journal",

issn = "0947-6539",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "14",

}

TY - JOUR

T1 - Diversity-oriented peptide stapling

T2 - a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy

AU - Tran, Thu Phuong

AU - Larsen, Christian Ørnbøl

AU - Røndbjerg, Tobias

AU - de Foresta, Martina

AU - Kunze, Micha Ben Achim

AU - Marek, Ales

AU - Hartvig Løper, Jacob

AU - Boyhus, Lotte-Emilie

AU - Knuhtsen, Astrid

AU - Lindorff-Larsen, Kresten

AU - Pedersen, Daniel Sejer

PY - 2017/3/8

Y1 - 2017/3/8

N2 - 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 azide-modified 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.

AB - 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 azide-modified 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.

U2 - 10.1002/chem.201700128

DO - 10.1002/chem.201700128

M3 - Journal article

C2 - 28106305

SN - 0947-6539

VL - 23

SP - 3490

EP - 3495

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

IS - 14

ER -

Diversity-oriented peptide stapling: a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater