N-Terminal dual protein functionalization by strain-promoted alkyne-nitrone cycloaddition

Strain-promoted alkyne-nitrone cycloadditon (SPANC) was optimized as a versatile strategy for dual functionalization of peptides and proteins. The usefulness of the dual labeling protocol is first exemplified by the simultaneous introduction of a chloroquine and a stearyl moiety, two endosomal escap...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2013-05, Vol.11 (17), p.2772-2779
Main Authors: Temming, Rinske P, Eggermont, Loek, van Eldijk, Mark B, van Hest, Jan C M, van Delft, Floris L
Format: Article
Language:English
Subjects:
Alkynes - chemistry
Biotin - chemistry
Click Chemistry
Cyclization
Green Fluorescent Proteins - chemistry
Humans
Lactoferrin - chemistry
Models, Molecular
Molecular Structure
Nitrogen Oxides - chemistry
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Summary:Strain-promoted alkyne-nitrone cycloadditon (SPANC) was optimized as a versatile strategy for dual functionalization of peptides and proteins. The usefulness of the dual labeling protocol is first exemplified by the simultaneous introduction of a chloroquine and a stearyl moiety, two endosomal escape-improving functional groups, into the cell-penetrating peptide hLF (human lactoferrin). Additionally, we demonstrate that dual labeling of proteins is feasible by combining metal-free and copper-catalyzed click chemistry. First, SPANC is applied to enhanced green fluorescent protein to introduce both biotin and a terminal alkyne. The terminal acetylene then serves as a convenient anchor point for the CuAAC reaction with azido-containing fluorescein, thereby demonstrating the potential of combined SPANC and CuAAC for the straightforward, dual functionalization of proteins.
ISSN:1477-0520
1477-0539
DOI:10.1039/c3ob00043e