The "two-headed" peptide inhibitors of interleukin-1 action

Two peptide fragments of IL-I family proteins, ITGSE and VTKFYF compete wit h IL-I for the cellular receptor. We synthesized a series of peptides compo sed of the sequences ITGSE and VTKFYK bound directly to each other or conne cted by such linkers as (Gly)(n), L- and D-Pro residues, Glu and Lys residu es (with peptide bond formed by main amino and carboxy groups or by side ch ain groups), and p-alanine and its homologues. Peptide IX with a gamma -Glu linker was the most potent inhibitor of IL-1 action. It was twice as poten t as both of the peptides indicated. (C) 2000 Published by Elsevier Science Inc.