Authors: B-C Lee and R.N. Zuckermann
Affilation: The Molecular Foundry, Lawrence Berkeley National Laboratory, United States
Pages: 28 - 31
Keywords: self-assembly, peptoids, biomimetic, foldamer, helix, non-natural oligomer
Peptoids are a novel class of non-natural biopolymer based on an N-substituted glycine backbone that are ideally suited for nanomaterials research. This bioinspired material has many unique properties that bridge the gap between proteins and bulk polymers. Like proteins, they are a sequence-specific heteropolymer, capable of folding into specific shapes and exhibiting potent biological activities; and like bulk polymers they are chemically and biologically stable and relatively cheap to make. Peptoids are efficiently assembled via automated solid-phase synthesis from hundreds of chemically diverse building blocks, allowing the rapid generation of huge combinatorial libraries. This provides a platform to discover nanostructured materials capable of protein-like molecular recognition and function. We present here the synthesis of a single-chain folded peptoid tertiary structure, which is capable of binding zinc ion specifically and with nanomolar affinity. By incorporating fluorescent reporter groups at various positions in the structure, we were able to use fluorescence resonance energy transfer (FRET) to probe the tertiary structure. This data, in combination with circular dichroism measurements, show that we have successfully constructed a completely non-natural tertiary fold from a single chain that is capable of specific molecular recognition.