Noncovalent Template-Assisted Mimicry of Multiloop Protein Surfaces: Assembling Discontinuous and Functional Domains

We report here a novel noncovalent synthetic strategy for template-assembled de novo protein design. In this approach, a peptide was first conjugated with two oligoguanosine strands via click chemistry and the conjugates were then self-assembled in the presence of metal ions. G-quadruplex formation directs two peptide strands to assemble on one face of the scaffold and form an adjacent two loop surface. This approach can be. used to rapidly prepare multiple two-loop structures with both homo- and heterosequences.