title: Biomimetic nanostructures: creating a high-affinity zinc-binding site in a folded nonbiological polymer.
abstract: One of the long-term goals in developing advanced biomaterials is to generate protein-like nanostructures and functions from a completely nonnatural polymer. Toward that end, we introduced a high-affinity zinc-binding function into a peptoid (N-substituted glycine polymer) two-helix bundle. Borrowing from well-understood zinc-binding motifs in proteins, thiol and imidazole moieties were positioned within the peptoid such that both helices must align in close proximity to form a binding site. We used fluorescence resonance energy transfer (FRET) reporter groups to measure the change of the distance between the two helical segments and to probe the binding of zinc. We systematically varied the position and number of zinc-binding residues, as well as the sequence and size of the loop that connects the two helical segments. We found that certain peptoid two-helix bundles bind zinc with nanomolar affinities and high selectivity compared to other divalent metal ions. Our work is a significant step toward generating biomimetic nanostructures with enzyme-like functions.
authors.affiliation: Biological Nanostructures Facility, The Molecular Foundry, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA.
authors.forename: Byoung-Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Tammy K
authors.initials: TK
authors.lastname: Chu
authors.forename: Ken A
authors.initials: KA
authors.lastname: Dill
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Zuckermann
mesh_terms: D001665:Binding Sites; D040761:Biomimetic Materials / Q000737:chemistry*; D032701:Biomimetics / Q000379:methods*; D031541:Fluorescence Resonance Energy Transfer; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D015032:Zinc / Q000737:chemistry*
chemical_list: D010455:Peptides; D011108:Polymers; C011080:polyglycine; D015032:Zinc