The observed correlation between sidechain diversity and structural uniqueness, coupled with the small variety of proteinogenic sidechains, suggests that incorporation of unnatural aminoacids should provide a powerful new mechanism for increased control over coiled-coil structure. Although it should be emphasized that any simple hydrocarbon substructure could exhibit interesting folding patterns, preliminary targets are focused on subtle perturbation of standard sidechains through introduction of branched, cyclic, unsaturated, or aromatic substructures. While discovery of new coiled-coil structures is interesting in and of itself, the attendant increase in future design precision has implications for a variety of biological applications. In principle any of the innumerable systems which employ coiled-coil recognition motifs could be investigated using the above approach. Single heptad from the dimeric coiled-coil region of GCN4.
Dotted line indicates salt-bridge observed in crystal structure.
All figures prepared with Molscript and Raster3D . Small peptides corresponding to this region of the C-terminus are known HIV inhibitors. Biologically Relevant Molecules Encapsulating the confluence of non-covalent forces governing biological recognition within the confines of a synthetic receptor is an ongoing challenge to chemical biology. Binding of short peptide fragments, a minimum bio-relevant substructure, has proven especially difficult. Pioneering efforts of Still and coworkers have produced hosts whose ligands were selected from combinatorial peptide libraries.