Examination of “Primary”, “Secondary”, and “Tertiary” Structural Elements of Bis-Amino Acids: Progress toward “Fauxteins”

by Matthew Parker

Institution: University of Pittsburgh
Year: 2015
Posted: 02/05/2017
Record ID: 2129236
Full text PDF: http://d-scholarship.pitt.edu/26065/1/MFLPTHESIS08%3A27.pdf


Proteins are in a category all their own as supramolecular entities enriched with both chirality and functionality. Inspired by them, we have created a new class of building blocks, called Bis-Amino Acids, for making molecules several kilodaltons in size that possess high degrees of both functionality and chirality. Bis-amino acids can assemble into shape-programmable macromolecules, called Spiroligomers that connect through pairs of amide bonds. They serve as water-soluble, rigid scaffolds capable of presenting collections of functional groups in different spatial orientations by virtue of their sequence, shape and stereochemistry of each chiral building block. This dissertation utilizes these unique building block as scaffolding for the presentation of functional groups in localized domains. A short spiroligomer sequence is used to presents a donor and acceptor pair facially for measuring electron-transfer in water. The same cleft motif is used to present a pair of hydrogen bonding donors to catalyze an aromatic Claisen rearrangement. Methods are developed to improve and expand the chemistry to make the bis-amino acids as well as their assembly into spiroligomers. Lastly, spiroligomers are utilized as intermediate building materials forming sequences of two and three connected by short, flexible linkers and cross-linked them into assemblies. We envision the use of these macromolecules, called “Fauxteins” to position multiple functional groups over large surface areas for mimicry of protein-protein interactions, recreation of complex active sites of enzymes, and form unique, chiral pockets for host-guest molecular recognition.