Crystallographic characterization of helical secondary structures in 2:1 and 1:2 α/Β-peptides

Soo Hyuk Choi, Ilia A. Guzei, Lara C. Spencer, Samuel H. Gellman

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Oligomers containing both α- and β-amino acid residues ("α/β-peptides") are intriguing as potential foldamers. A large set of α/β-peptide backbones can be generated by combining α and β-amino acid residues in different patterns; however, most research to date has focused on the simplest pattern, 1:1 α:β. We have begun to explore the range of variation that can be achieved with α-residue/β-residue combinations by examining the folding behavior of oligomers that contain 2:1 and 1:2 α:β patterns. The β-residues in our systems have a five-membered-ring constraint (trans-2- aminocyclopentanecarboxylic acid (ACPC) residues), because these preorganized subunits strongly promote helical folding for 1:1 α/α backbones and pure β backbones. Previously we concluded that two helical conformations are available to 2:1 and 1:2 α/β-peptides containing ACPC or analogously constrained β-residues, one helix defined by i,i+3 C=O ⋯H-N backbone hydrogen bonds and the other defined i,i+4 C=O⋯-H-N hydrogen bonds. These deductions were based on 2D NMR analysis of a 2:1 heptamer and a 1:2 hexamer in methanol. Crystallographic analysis of a pair of analogous nonpolar α/β-peptides showed only the i,i+3 hydrogen-bonded helical conformations. We now report four new crystal structures of 2:1 α/β-peptides, ranging in length from 5 to 11 residues, and six new crystal structures of 1:2 α//3-peptides, ranging in length from 6 to 10 residues. All 10 of these new structures are fully helical, and all helices display the i,i+3 C=O⋯H-N hydrogen bonding pattern. These crystallographic data sets, collectively, provide high structural definition for the i,i+3 hydrogen-bonded helical secondary structures available to these foldamer backbones.

Original languageEnglish
Pages (from-to)2917-2924
Number of pages8
JournalJournal of the American Chemical Society
Volume131
Issue number8
DOIs
Publication statusPublished - 2009 Mar 4

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Peptides
Hydrogen
Cycloleucine
Hydrogen bonds
Oligomers
Conformations
Amino acids
Crystal structure
Amino Acids
Acids
Hydrogen Bonding
Methanol
Nuclear magnetic resonance
Research

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Choi, Soo Hyuk ; Guzei, Ilia A. ; Spencer, Lara C. ; Gellman, Samuel H. / Crystallographic characterization of helical secondary structures in 2:1 and 1:2 α/Β-peptides. In: Journal of the American Chemical Society. 2009 ; Vol. 131, No. 8. pp. 2917-2924.
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Crystallographic characterization of helical secondary structures in 2:1 and 1:2 α/Β-peptides. / Choi, Soo Hyuk; Guzei, Ilia A.; Spencer, Lara C.; Gellman, Samuel H.

In: Journal of the American Chemical Society, Vol. 131, No. 8, 04.03.2009, p. 2917-2924.

Research output: Contribution to journalArticle

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