Design and Synthesis of Backbone Cyclic Phosphopeptides: The IκB Model
We present the development and synthesis of a backbone cyclic (BC) phosphoserine-containing library. For our model, we used the conserved sequence derived from Inhibitor kappa B (IκB) that inhibits the interaction between IκB and the β-transduction repeat-containing protein (β-TrCp). Backbone cyclization is a method for conferring metabolic stability and enhanced bioavailability on a chosen biologically active sequence. Cycloscan is a method in which a library is designed using a single parent sequence but differing BC ring closures to allow the biologically active sequence conformational diversity. A selective and metabolically stable BC peptide may be identified from such a library . Phosphopeptides are potential inhibiters of the kinome, the subset of the genome consisting of the protein kinase genes , but are synthetically challenging.
We applied the backbone cyclization strategy to find a peptide that inhibits nuclear factor-kappa B (NF-κB). NF-κB is a latent...
KeywordsBinding Pocket Secondary Amine Cyclic Peptide Peptide Library Protein Kinase Gene
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