MOLECULAR OPTICAL RAILS BASED ON Aib Modular Chemistry with Unusually Reliable Peptide Helices

摘要

Well established properties of peptide helices most often must be understood in the context of folding/unfolding temperatures and conformational equilibria. This limits their general usefulness as structurally well-defined modules. The conformational imperatives of the peptide backbone can be transformed, however, by the use of a-aminoisobutyric acid (Aib), whose geminal dimethyl functionality provides an unforgiving steric hindrance enforcing a well-defined helical backbone conformation. The corresponding unfolded state is unknown. The sequence composition and patterns required to attain this highly stable helix are described, as well as the ID and 2D NMR evidence in solvents ranging from the benign CDCI3 to the more aggressive DMSO. Temperature studies up to 150 °C are summarized. The utility of these helices has been considerably expanded in the direction of optical and electronic versatility by the design and synthesis of aromatic cc-amino acids in which electron-rich and electron-deficient aromatic rings are fused to carbocylic structures incorporating the a-carbon. These aromatics possess the same oc,a -dialkylation as the parent Aib and exhibit the same helical backbone propensity. These properties enable a modular strategy for the incorporation of electronic and optical functionality into variable sequence positions along an unchanging molecular optical rail.