Accommodation of α-substituted residues in the β-peptide 12-helix: Expanding the range of substitution patterns available to a foldamer scaffold

Jin Seong Park, Hee Seung Lee, Jonathan R. Lai, Byeong Moon Kim, Samuel H. Gellman

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

β-Amino acid oligomers composed exclusively of homochiral trans-2-aminocyclopentanecarboxylic acid (ACPC) residues and/or related pyrrolidine-based residues are known to favor a specific helical secondary structure that is defined by 12-membered ring C=O(i)- -H - N(i+3) hydrogen bonds ("12-helix"). The 12-helix is structurally similar to the familiar α-helix and therefore represents a source of potential α-helix-mimics. The 12-helix will be most useful in this regard if this conformational scaffold can be employed to arrange specific sets of protein-like side chains in space. Here we examine whether the 12-helix tolerates insertion of acyclic β-amino acid residues bearing a substituent in the α-position ("β2-residues"). Seventeen homologous β-peptide heptamers have been prepared in which one to four β2-residues reside among ACPC and/or pyrrolidine residues. Circular dichroism comparisons suggest that β2-residues have a lower 12-helical propensity than do residues preorganized by a five-membered ring, as expected, but that β-peptides containing β2-residues at one or two of the seven positions retain a significant preference for 12-helix formation. These results indicate that a limited number of β2-residues can be used to introduce side chains at specific positions along the surface of a 12-helix.

Original languageEnglish (US)
Pages (from-to)8539-8545
Number of pages7
JournalJournal of the American Chemical Society
Volume125
Issue number28
DOIs
StatePublished - Jul 16 2003
Externally publishedYes

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Cycloleucine
Scaffolds
Acyclic Acids
Peptides
Amino acids
Substitution reactions
Bearings (structural)
Amino Acids
Acids
Dichroism
Circular Dichroism
Oligomers
Hydrogen
Hydrogen bonds
Proteins
pyrrolidine

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Accommodation of α-substituted residues in the β-peptide 12-helix : Expanding the range of substitution patterns available to a foldamer scaffold. / Park, Jin Seong; Lee, Hee Seung; Lai, Jonathan R.; Kim, Byeong Moon; Gellman, Samuel H.

In: Journal of the American Chemical Society, Vol. 125, No. 28, 16.07.2003, p. 8539-8545.

Research output: Contribution to journalArticle

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