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Title: Accessing sequence specific hybrid peptoid oligomers with varied pendant group spacing

Journal Article · · European Polymer Journal
 [1];  [2];  [3];  [3]
  1. University of Michigan, Ann Arbor, MI (United States); Bowling Green State University, OH (United States)
  2. University of Michigan, Ann Arbor, MI (United States); HAN University of Applied Sciences, Nijmegan (Netherlands)
  3. University of Michigan, Ann Arbor, MI (United States)
+ Show Author Affiliations

The synthesis of β-peptoids (i.e., N-substituted β-alanine oligomers) 10 or more residues in length has proven challenging owing to poor coupling efficiency even after extended reaction times, resulting in the substantial generation of deletion sequences and consequently making purification of the target oligomer challenging. To overcome the limitations of conventional approaches, in this report we examine a synthetic method to rapidly yield sequence specific β- and γ-peptoids with 4–20 repeat units in high purity via alternating monomer addition and deprotection reactions using Fmoc-protected, N-substituted β-alanine- and γ-aminobutyric acid-based monomers in conjunction with microwave-assisted automated solid phase synthesis. By decoupling the secondary amine generation and the oligomer synthesis, this approach circumvents the relatively low reaction efficiency of primary amine alkylation with halogenated propionic or butyric acid to afford secondary amines while retaining the pendant group chemical diversity offered by α-peptoids. We establish the compatibility of this technique with conventional Fmoc-peptide and ‘submonomer’ peptoid syntheses by fabricating several hybrid oligomer sequences including long β- and γ-peptoid oligomers in addition to hybrid α/β, β/peptide, and α/β/γ-systems, thereby confirming the capacity for this approach to yield oligomers with a backbone spacing of three or more atoms between any two residues. Additionally, we demonstrate that mixtures of aromatic amine- and aldehyde-bearing β-peptoids undergo rapid dynamic covalent assembly to afford oligomeric molecular ladders.

Research Organization:
Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF)
Grant/Contract Number:
SC0012479
OSTI ID:
1611824
Alternate ID(s):
OSTI ID: 1775757
Journal Information:
European Polymer Journal, Vol. 118, Issue C; ISSN 0014-3057
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 7 works
Citation information provided by
Web of Science

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