Accommodation of alpha-substituted residues in the beta-peptide 12-helix: expanding the range of substitution patterns available to a foldamer scaffold.
Beta-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 alpha-helix and therefore represents a source of potential alpha-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 beta-amino acid residues bearing a substituent in the alpha-position ("beta(2)-residues"). Seventeen homologous beta-peptide heptamers have been prepared in which one to four beta(2)-residues reside among ACPC and/or pyrrolidine residues. Circular dichroism comparisons suggest that beta(2)-residues have a lower 12-helical propensity than do residues preorganized by a five-membered ring, as expected, but that beta-peptides containing beta(2)-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 beta(2)-residues can be used to introduce side chains at specific positions along the surface of a 12-helix.
Park
Jin-Seong
JS
School of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea.
Lee
Hee-Seung
HS
Lai
Jonathan R
JR
Kim
Byeong Moon
BM
Gellman
Samuel H
SH
D002942:Circular Dichroism; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
D009842:Oligopeptides; D003515:Cycloleucine; C065594:cispentacin