Reason: Restricted by author. A copy can be supplied under Section 51(2) of the Australian Copyright Act 1968 by submitting a document delivery request through your library or by emailing firstname.lastname@example.org
Novel 14-helical functionalised β3-peptides
In order to distinguish essays and pre-prints from academic theses, we have a separate category. These are often much longer text based documents than a paper.
posted on 06.02.2017by Gopalan, Romila Devi
β3-Peptides, (oligomers of β3-amino acids) are among the most widely studied unnatural peptides at present, due to their ability to adopt discrete and stable secondary helical structures. Of the many types of helices formed by β3-peptides, 14-helices are particularly interesting as they have 3 residues per helical turn (with a pitch of 5.0Å) and are stabilised by 14-membered hydrogen bonding rings. This allows the side chains to be aligned perfectly in three faces. The residues at positions i/i+3 are not only on the same face of the helix but are also are relatively close to each other. The aim of this study was to design and synthesise novel 14-helical stapled β3-peptides on which further functionalisation of the stapled face of the helix can be performed and used to create novel peptide assemblies. β3-Peptides were synthesised by incorporating O-allyl-β3-serines and allyl-β3-glycines at i/i+3 positions and efficiently stapling the allyl groups via ring closing metathesis (RCM) on a solid support. Further functionalisation was also performed on the alkene moiety of the staple with established alkene chemistry. The CD and NMR spectroscopic studies showed that β3-peptides, unstapled, stapled as well as functionalised staple, exhibited 14-helix signatures. These results indicate the stability of the 14-helical conformation in β3-peptides irrespective of the modification performed on the peptide. Crystallographic studies also confirms that the unstapled, stapled or functionalised staple in β3-peptides are not only 14-helical but that they assemble into ‘super-helices’. These are nanorod-like structures which self-assemble axially through three intermolecular hydrogen bonds between adjacent peptides. The crystal packing also showed that ‘super-helices’ or nanorods arranged in antiparallel sheets and are held together by hydrophobic interactions and apparently a critical hydrogen bonding between antiparallel nanorods. These findings suggest that 14-helical β3-peptides are very stable and can be structurally manipulated without altering its folding conformation or the binding motifs. Thus, 14-helical β3-peptides can be used to generate a library of new molecules of biological significance.