Diversity-oriented peptide stapling: a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy
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Diversity-oriented peptide stapling : a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy. / Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias; de Foresta, Martina; Kunze, Micha Ben Achim; Marek, Ales; Hartvig Løper, Jacob; Boyhus, Lotte-Emilie; Knuhtsen, Astrid; Lindorff-Larsen, Kresten; Pedersen, Daniel Sejer.
I: Chemistry: A European Journal, Bind 23, Nr. 14, 08.03.2017, s. 3490-3495.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
N1 - © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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, that 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, that 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
VL - 23
SP - 3490
EP - 3495
JO - Chemistry: A European Journal
JF - Chemistry: A European Journal
SN - 0947-6539
IS - 14
ER -
ID: 172638389