Application of copper(I) catalyzed azide-alkyne [3+2] cycloaddition to the synthesis of template-assembled multivalent peptide conjugates.
Here we describe the facile generation of tetravalent peptide conjugates via a copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) using a cyclic peptide template as a versatile conjugation scaffold. This stable and rigid framework is a conformationally constrained cyclic beta-sheet decorated with spatially defined alkyne moieties that serve as selectively addressable coupling sites. The proposed method allows for the effective coupling of unprotected peptide monomers in water at room temperature within comparatively short reaction times. The resulting conjugates display the ligands in an oriented manner, thus allowing for multivalent interactions with given target molecules, which may contribute to enhanced affinity and specificity. In addition, the selected scaffold offers an orthogonal coupling site for the incorporation of fluorescent labels or radioligands.
Clemens-Schöpf Institute of Organic Chemistry and Biochemistry, Darmstadt University of Technology, Petersenstr. 22, 64287, Darmstadt, Germany.
Olga
O
Avrutina
Martin
M
Empting
Sebastian
S
Fabritz
Matin
M
Daneschdar
Holm
H
Frauendorf
Ulf
U
Diederichsen
Harald
H
Kolmar
D000480:Alkynes / Q000737:chemistry*; D000595:Amino Acid Sequence; D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D008024:Ligands; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*
D000480:Alkynes; D001386:Azides; D005456:Fluorescent Dyes; D008024:Ligands; D010456:Peptides, Cyclic; C009055:propargylglycine; D003300:Copper; D005998:Glycine