Bundle-forming α-helical peptide–dendron hybrid

Abstract

Peptides and dendrons are enticing building blocks from which to construct hybrid macromolecules because each can be prepared as monodisperse and sequence defined materials. Folding and assembly properties designed into the amino acid sequence of a peptide-dendron hybrid manifest in the formation of a dendronized bundle of α-helices.

Synthesis and Self-Assembly of Bundle-Forming α-Helical Peptide–Dendron Hybrids

“…Peptide 3b required double couplings at Leu5 and Leu12, and peptide 5b required double couplings at Leu6 and Leu13. The key differences between the manual 17b and automated syntheses 15 have to do with the coupling reaction conditions. In the manual synthesis the N α -Fmoc-protected amino acids are activated with HBTU/HOBt and diisopropylethylamine as the base ([HBTU] 0 /[HOBt] 0 /[DIEA] 0 /[Fmoc-AA-OH] 0 = 0.9/1/2/1; [Fmoc-AA-OH] 0 = 0.5 M).…”

“…The CD spectra in Figure 4 were recorded under conditions where each of the compounds is maximally folded, so the intensity of each spectrum directly reports on the effect of the changes to the surface residues. We calculated from [θ] 222 values in each spectrum that hybrid 1a is 76% as α-helical as 5a 15 and hybrid 2 is 63% as helical as 5a . A significant contribution to the decreased helicity comes from steric interactions between the dendrons, especially between the peripheral groups.…”

“…Compounds 6-11 , peptide-dendron hybrid 1a , peptide 3a and Ac-YLKKLLKLLKKLLK-NH 2 ( 5a ) were prepared according to literature procedures. 17 Peptides were assembled by manual 17b or automated 15 solid-phase peptide synthesis according to general protocols. Peptide concentration and salt titration CD experiments were done according to previously described general protocols.…”

“…Peptide concentration and salt titration CD experiments were done according to previously described general protocols. 15 …”

Peptide–dendron hybrids that adopt sequence-encoded β-sheet conformations

“…Inspired by the tunability and processability afforded by combinations of peptides with dendrons, we have investigated hybrids of dendrons with an α-helical bundle-forming peptide. 32, 33, 54, 55 The defined arrangement of different amino acids in the core of an α-helix bundle motif could allow us to synthesize chemical gradients or unique binding sites within supramolecular dendrimers. We recently reported examples of α-helix bundle-forming peptide-dendron hybrids that self-organize in an hexagonally ordered array of columns.…”