| Proteins are biological macromolecules with a diverse set of complex functions. Well defined structures are fundamental to the numerous functions exhibited by proteins (e.g., cell signaling, catalysis). However, design of these complex molecules has been challenging. One approach to creating molecules with functions similar to those of proteins is to reduce the molecular complexity of the molecules. Such simplification eases the difficulty inherent in designing any complex molecule, but often at the cost of functional efficiency. One class of simplified protein mimics, foldamers, has had success in mimicking natural (and manifesting unnatural) structures and functions.;This thesis describes our work on expanding the universe of known foldamer functionality using beta- and alpha/beta-peptides. Chapter 2 evaluates a combinatorial approach to designing an alpha/beta-peptide that binds to the anti-apoptotic proteins Bcl-xL and Mcl-1; Mcl-1 had proven incompatible with previously-designed foldamer ligands. The focus then shifts to the development of the first catalytic foldamer with the discovery of a beta-peptide with retroaldolase activity (Chapter 3). Chapter 4 describes efforts aimed at designing a unique bifunctional foldamer organocatalyst. Chapter 5 returns to the principles learned in Chapter 3 to search for additional enzyme-catalyzed reactions that would be amenable to beta-peptide catalysis. Chapter 6 summarizes and translates the work presented in the previous chapters into language more accessible to non-scientists. |
