A Nonpeptidic Reverse Turn that Promotes Parallel Sheet Structure Stabilized by CH⋅⋅⋅O Hydrogen Bonds in a Cyclopropane γ‐Peptide

Evaluation of a Cyclopentane-Based γ-Amino Acid for the Ability to Promote α/γ-Peptide Secondary Structure

“…1b,d These trends were subsequently confirmed by Seebach et al, who also identified an α,β,γ-trisubstitution pattern that promotes a helical conformation (Figure 1a). 1c,f,h Incorporation of cyclic constraints into the γ-amino acid backbone can promote sheet 1a,g,j,k or helix secondary structure, depending on the ring size, the configurations of the stereogenic centers, and the location of the ring within the γ residue (i.e., incorporation of the Cα-Cβ bond, or the Cβ-Cγ bond, or both the Cα-Cβ and Cβ-Cγ bonds into the ring).1 Although initial studies focused on the folding of pure γ-peptide backbones, subsequent efforts have expanded to include heterogeneous backbones, in which γ residues are combined with α and/or β residues, to generate α/γ − , β/γ − or α/β/γ-peptides.3…”

“…Thus, using a ring to constrain one backbone bond within a γ residue may not be sufficient to encode a strong and specific folding propensity. 1 …”

“…1,2 Pioneering work by Hanessian et al showed that the folding behavior of γ-amino acid residues bearing one substituent at the α carbon and another at the γ carbon was critically dependent on the relative configurations at the two stereocenters, with one stereoisomeric form supporting helical secondary structure and the other stereoisomeric form favoring reverse turn secondary structure. 1b,d These trends were subsequently confirmed by Seebach et al, who also identified an α,β,γ-trisubstitution pattern that promotes a helical conformation (Figure 1a).…”

“…1,2 Pioneering work by Hanessian et al showed that the folding behavior of γ-amino acid residues bearing one substituent at the α carbon and another at the γ carbon was critically dependent on the relative configurations at the two stereocenters, with one stereoisomeric form supporting helical secondary structure and the other stereoisomeric form favoring reverse turn secondary structure. 1b,d These trends were subsequently confirmed by Seebach et al, who also identified an α,β,γ-trisubstitution pattern that promotes a helical conformation (Figure 1a). 1c,f,h Incorporation of cyclic constraints into the γ-amino acid backbone can promote sheet 1a,g,j,k or helix secondary structure, depending on the ring size, the configurations of the stereogenic centers, and the location of the ring within the γ residue (i.e., incorporation of the Cα-Cβ bond, or the Cβ-Cγ bond, or both the Cα-Cβ and Cβ-Cγ bonds into the ring).1 Although initial studies focused on the folding of pure γ-peptide backbones, subsequent efforts have expanded to include heterogeneous backbones, in which γ residues are combined with α and/or β residues, to generate α/γ − , β/γ − or α/β/γ-peptides.3…”

Dissection of the Factors Affecting Formation of a CH∙∙∙O H-Bond. A Case Study

“…Recent work [67] has shown for example, that a CH··O HB can override the normal trans-planar conformational preferences of α-fluoroamides. In the biological realm too, CH···O HBs play quite an important role [53,[68][69][70][71][72][73][74][75] in systems varying from interhelical interactions in proteins to structures of oligosaccharides and carbohydrates and nucleic acids [76][77][78][79]. There is some evidence that CH··O HBs may play a previously overlooked role in the structure of such protein stalwarts as the β-sheet [80,81].…”