Crystallographic characterization of helical secondary structures in 2:1 and 1:2 alpha/beta-peptides.
Oligomers containing both alpha- and beta-amino acid residues ("alpha/beta-peptides") are intriguing as potential foldamers. A large set of alpha/beta-peptide backbones can be generated by combining alpha- and beta-amino acid residues in different patterns; however, most research to date has focused on the simplest pattern, 1:1 alpha:beta. We have begun to explore the range of variation that can be achieved with alpha-residue/beta-residue combinations by examining the folding behavior of oligomers that contain 2:1 and 1:2 alpha:beta patterns. The beta-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 alpha:beta backbones and pure beta backbones. Previously we concluded that two helical conformations are available to 2:1 and 1:2 alpha/beta-peptides containing ACPC or analogously constrained beta-residues, one helix defined by i,i+3 CO...H-N backbone hydrogen bonds and the other defined by i,i+4 CO...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 alpha/beta-peptides showed only the i,i+3 hydrogen-bonded helical conformations. We now report four new crystal structures of 2:1 alpha/beta-peptides, ranging in length from 5 to 11 residues, and six new crystal structures of 1:2 alpha/beta-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 CO...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.
Choi
Soo Hyuk
SH
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Guzei
Ilia A
IA
Spencer
Lara C
LC
Gellman
Samuel H
SH
D000596:Amino Acids / Q000737:chemistry*; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003515:Cycloleucine / Q000737:chemistry*; D006860:Hydrogen Bonding; D007536:Isomerism; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D009842:Oligopeptides; D003515:Cycloleucine; C100049:2-aminoisobutyric acid