916885-51-3Relevant academic research and scientific papers
Strengthening Peptoid Helicity through Sequence Site-Specific Positioning of Amide cis-Inducing NtBu Monomers
Jouffret, Laurent,Khiari, Jameleddine,Kriznik, Alexandre,Roy, Olivier,Rzeigui, Maha,Taillefumier, Claude,Traikia, Mounir
, (2020)
The synthesis of biomimetic helical secondary structures is sought after for the construction of innovative nanomaterials and applications in medicinal chemistry such as the development of protein-protein interaction modulators. Peptoids, a sequence-defined family of oligomers, enable a peptidomimetic strategy, especially considering the easily accessible monomer diversity and peptoid helical folding propensity. However, cis-trans isomerization of the backbone tertiary amides may impair the peptoid's adoption of stable secondary structures, notably the all-cis polyproline I-like helical conformation. Here, we show that cis-inducing NtBu achiral monomers strategically positioned within chiral sequences may reinforce the degree of peptoid helicity, although with a reduced content of chiral side chains. The design principles presented here will undoubtedly help achieve more conformationally stable helical peptoids with desired functions.
Homogeneous and Robust Polyproline Type i Helices from Peptoids with Nonaromatic α-Chiral Side Chains
Roy, Olivier,Dumonteil, Geoffrey,Faure, Sophie,Jouffret, Laurent,Kriznik, Alexandre,Taillefumier, Claude
supporting information, p. 13533 - 13540 (2017/10/05)
Peptoids that are oligomers of N-substituted glycines represent a class of peptide mimics with great potential in areas ranging from medicinal chemistry to biomaterial science. Controlling the equilibria between the cis and trans conformations of their backbone amides is the major hurdle to overcome for the construction of discrete folded structures, particularly for the development of all-cis polyproline type I (PPI) helices, as tools for modulating biological functions. The prominent role of backbone to side chain electronic interactions (n → π) and side chains bulkiness in promoting cis-amides was essentially investigated with peptoid aromatic side chains, among which the chiral 1-naphthylethyl (1npe) group yielded the best results. We have explored for the first time the possibility to achieve similar performances with a sterically hindered α-chiral aliphatic side chain. Herein, we report on the synthesis and detailed conformational analysis of a series of (S)-N-(1-tert-butylethyl)glycine (Ns1tbe) peptoid homo-oligomers. The X-ray crystal structure of an Ns1tbe pentamer revealed an all-cis PPI helix, and the CD curves of the Ns1tbe oligomers also resemble those of PPI peptide helices. Interestingly, the CD data reported here are the first for any conformationally homogeneous helical peptoids containing only α-chiral aliphatic side chains. Finally we also synthesized and analyzed two mixed oligomers composed of NtBu and Ns1tbe monomers. Strikingly, the solid state structure of the mixed oligomer Ac-(tBu)2-(s1tbe)4-(tBu)2-COOtBu, the longest to be solved for any linear peptoid, revealed a PPI helix of great regularity despite the presence of only 50% of chiral side chain in the sequence.
Azabicyclic amino acids by stereoselective dearomatizing cyclization of the enolates of N-nicotinoyl glycine derivatives
Arnott, Gareth,Clayden, Jonathan,Hamilton, Stuart D.
, p. 5325 - 5328 (2007/10/03)
On activation by pyridine N-acylation, enolates of N-nicotinoyl and N-isonicotinoyl glycine and alanine derivatives cyclize to yield 6,5-azabicyclic or 6,4-azaspirocyclic lactams. With an N-α-methyl-p-methoxybenzyl group the cyclization is diastereoselect
