Studies on the structural features of the versatile peptide foldamers

Abstract

In nature system, folding is one of the crucial process that nature has selected to control the conformation of molecule, so that enables to carry out chemical functions such as information storage, enzyme and catalyst. To interpret and mimic the structural and functional behavior of biopolymer in natural system, artificial folded molecular architecture, defined as “foldamer”, could mimic the secondary structure of protein. Additionally, the versatile functions of foldamers regarding their structure have been established by self-assembly. Enormous structural information of protein is stored in polypeptide sequence provides a clear understanding of the interplay between the structure and functions. Based on this fact, studies on the structural features of the versatile peptide foldamers could be utilized to construct protein like artificial complex, showing a biological and catalytic functions.

This dissertation is focused on the two main topics that are directing foldamer self-assembly with a cyclopropanoyl cap and studies on foldamers containing tetrahydrothiophene. In chapter 2, cyclopropanoyl cap was attached in alpha/beta peptide foldamer and through a combined analytical and computational investigation, cyclopropanoyl capping was observed to markedly enhance self-assembly in recalcitrant substrates and direct the formation of a single intermolecular N–H···O/Cα–H···O bonding motif in single crystals, regardless of peptide sequence or foldamer conformation. DFT calculations validated the experimental results that the N–H···O/Ca–H···O interaction created by the cap was sufficiently attractive to influence self-assembly. This strategy could be used to rational design of self-assembling organic materials for exploration of new substrates and speed up the development of novel applications within this increasingly important class of materials.

In chapter 3, by replacing the C4 carbon in the cyclopentane ring of (1S,2S)-2-Aminocyclopentane-1-carboxylic acid (ACPC) with sulfur, (3S,4R)-4-Aminotetrahydrothiophene-3-carboxylic acid (ATTC) was first reported and found that ATTC could act as a bioisostere of ACPC so that adapting 12-helical structure in a foldamer level. However sulfide group in ATTC, could be further oxidized into sulfone and sulfoxide through oxidation reaction. In addition, sulfide group was further utilized as a catalyst to mediate Corey-Chaykovsky reaction. This result implies that newly synthesized foldamer could grow inventory of the foldamer and widen the application of foldamer.