The study of short, autonomously folding peptides, or "miniproteins," is important for advancing our understanding of protein stability and folding specificity. Although many examples of synthetic alpha-helical structures are known, relatively few mixed alpha/beta structures have been successfully designed. Only one mixed-secondary structure oligomer, an alpha/beta homotetramer, has been reported thus far. In this report, we use structural analysis and computational design to convert this homotetramer into the smallest known alpha/beta-heterotetramer. Computational screening of many possible sequence/structure combinations led efficiently to the design of short, 21-residue peptides that fold cooperatively and autonomously into a specific complex in solution. A 1.95 A crystal structure reveals how steric complementarity and charge patterning encode heterospecificity. The first- and second-generation heterotetrameric miniproteins described here will be useful as simple models for the analysis of protein-protein interaction specificity and as structural platforms for the further elaboration of folding and function.
6-(2-Dimethylaminonaphthoyl) alanine (DANA) was prepared via an enantioselective synthesis and incorporated into the S-peptide of RNase S establishing the large changes in fluorescence that can occur upon peptide-protein interaction.
Enantioselective Synthesis and Application of the Highly Fluorescent and Environment-Sensitive Amino Acid 6-(2-Dimethylaminonaphthoyl) Alanine (DANA). -The title compound (V) is prepared via enantioselective alkylation of imine (II) in the presence of a chiral quaternary ammonium salt under phase-transfer conditions. -(NITZ, MARK; MEZO, ADAM R.; ALI, MAYSSAM H.; IMPERIALI, BARBARA;
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