Conformational Preferences in Synthetic Peptide Analogues

Abstract

This dissertation concerns the use of previously synthesised amino acids 1,1'-binaphthyl-substituted alpha-aminoisobutyric acid (Bin) and its biphenyl analogue (Bip) in the control and detection of helicity in alpha-aminoisobutyric acid (Aib) oligomers. The binaphthyl moiety of the Bin amino acid exhibits stable axial chirality, allowing for its use as an N-terminal promoter of helicity in Aib oligomers. However, slow interconversion between the two enantiomers of the Bip residue is observed at room temperature. Previous reports have confirmed that induction of axial chirality in the biphenyl moiety can occur with the attachment of a chiral amino acid; this phenomenon allows the Bip to act as a reporter of helicity. The synthesis of the Bin and Bip amino acids is described along with the required Aib oligomers. Incorporation of the Bin and Bip amino acids into Aib oligomers is then explored. With the necessary Aib-Bin/Bip peptides acquired, their ability as promoters and reporters of helicity can be studied with the use of 1H-NMR and CD spectroscopy. Results indicate that the Bin amino acid is the best promoter of helicity in Aib oligomers observed so far, an important step in the ongoing work of achieving 100% helical excess in Aib oligomers. Induction of axial-chirality in the biphenyl core of the Bip residue in an Aib oligomer was observed when an N-terminal controller was attached. The induced conformer of the Bip residue [(R)- and (S)-enantiomer] was found to be related to the direction of the helix.

Date of Award	31 Dec 2011
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jonathan Clayden (Supervisor)