Oligo(N-aryl glycines): a new twist on structured peptoids.
We explore strategies to enhance conformational ordering of N-substituted glycine peptoid oligomers. Peptoids bearing bulky N-alkyl side chains have previously been studied as important examples of biomimetic "foldamer" compounds, as they exhibit a capacity to populate helical structures featuring repeating cis-amide bonds. Substantial cis/trans amide bond isomerization, however, gives rise to conformational heterogeneity. Here, we report the use of N-aryl side chains as a tool to enforce the presence of trans-amide bonds, thereby engendering structural stability. Aniline derivatives and bromoacetic acid are used in the facile solid-phase synthesis of a diverse family of sequence-specific N-aryl glycine oligomers. Quantum mechanics calculations yield a detailed energy profile of the folding landscape and substantiate the hypothesis that the presence of anilide groups establishes a strong energetic preference for trans-amide bonds. X-ray crystallographic analysis and solution NMR studies verify this preference. Molecular modeling indicates that the linear oligomers can adopt helical structures resembling a polyproline type II helix. High resolution structures of macrocyclic oligomers incorporating both N-alkyl and N-aryl glycine units confirm the ability to direct the presence of trans-amide bonds specifically at N-aryl positions. These results are an important step in developing strategies for the rational de novo design of new structural motifs in biomimetic oligopeptoid systems.
Shah
Neel H
NH
Department of Chemistry, Center for Genomics & Systems Biology, New York University, New York, New York 10003, USA.
Butterfoss
Glenn L
GL
Nguyen
Khanh
K
Yoo
Barney
B
Bonneau
Richard
R
Rabenstein
Dallas L
DL
Kirshenbaum
Kent
K
D000083:Acetanilides / Q000737:chemistry; D000577:Amides / Q000737:chemistry; D032701:Biomimetics; D003198:Computer Simulation; D008958:Models, Molecular; D034442:N-substituted Glycines / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
D000083:Acetanilides; D000577:Amides; D034442:N-substituted Glycines; D011108:Polymers; C508827:acetanilide