title: Toward the synthesis of artificial proteins: the discovery of an amphiphilic helical peptoid assembly.
abstract: While nature exploits folded biopolymers to achieve molecular recognition and catalysis, comparable abiological heteropolymer systems have been difficult to create. We synthesized and identified abiological peptoid heteroploymers capable of binding a dye. Using combinatorial synthesis, we constructed a library of 3400 amphiphilic 15-mer peptoids on an ultra-high-capacity beaded support. Individual macrobeads, each containing a single peptoid sequence, were arrayed into plates, cleaved, and screened in aqueous solution to locate dye binding heteropolymer assemblies. Resynthesis and characterization demonstrated the formation of defined helical assemblies as judged by size-exclusion chromatography, circular dichroism, and analytical ultracentrifugation. Inspired by nature's process of sequence variation and natural selection, we identified rare abiological sequence-specific heteropolymers that begin to mimic the structure and functional properties of their biological counterparts.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Burkoth
authors.forename: Eric
authors.initials: E
authors.lastname: Beausoleil
authors.forename: Surinder
authors.initials: S
authors.lastname: Kaur
authors.forename: Dahzi
authors.initials: D
authors.lastname: Tang
authors.forename: Fred E
authors.initials: FE
authors.lastname: Cohen
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Zuckermann
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D005453:Fluorescence; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008970:Molecular Weight; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D019151:Peptide Library; D034444:Peptoids; D017510:Protein Folding; D020539:Sequence Analysis, Protein / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D014461:Ultracentrifugation
chemical_list: D009842:Oligopeptides; D019151:Peptide Library; D034444:Peptoids; D005998:Glycine