Macrocyclization enhances affinity of chemokine-binding peptoids
Kevin Brahm1, Julia S Wack1, Stefanie Eckes1
1Clemens-Schöpf-Institute of Organic Chemistry and Biochemistry, TU Darmstadt, Darmstadt, Germany.
Abstract:
Peptoids that bind to protein targets can be selected from one-bead-one-compound libraries. Macrocyclization has been often used to increase conformational rigidity and binding affinity in both peptides and peptoids. Here we describe a combined strategy to label and cyclize hexameric peptoid sequences previously identified in a screen against the inflammatory chemokine interleukin-8/CXCL8 that is involved in a number of inflammatory diseases. Cyclization can be performed on-bead in the presence of side-chain protecting groups so that this strategy can be applied to a large variety of sequences. The affinity of the resulting tetramethylrhodamine-labeled macrocyclic peptomers to CXCL8 is increased by at least 1 order of magnitude compared to the original linear sequences.
Related Concept Videos
Affinity and Avidity
The Equilibrium Binding Constant and Binding Strength
The Equilibrium Binding Constant and Binding Strength
Electron Affinity
Affinity Chromatography
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...


