Toward the synthesis of artificial proteins: the discovery of an amphiphilic helical peptoid assembly.
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.
Burkoth
Timothy S
TS
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
Beausoleil
Eric
E
Kaur
Surinder
S
Tang
Dahzi
D
Cohen
Fred E
FE
Zuckermann
Ronald N
RN
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
D009842:Oligopeptides; D019151:Peptide Library; D034444:Peptoids; D005998:Glycine