Peptidomimetics are synthetic oligomers that resemble the activities of peptides. Their advantages over peptides include high stability towards proteolysis and enormous chemical diversity. Over the past two decades, there have been extensive efforts to develop peptide mimics, such as beta-peptides, peptoids, D-peptides, etc. The research on peptidomimetics have led to many important applications in both medicinal and material science. In order to explore new functions, the discovery of peptidomimetics with novel frameworks is essential. We reported the synthesis and evaluation of a new class of peptidomimetics, termed as gamma-AApeptides. Previous studies of gamma-AApeptides have revealed that gamma-AApeptides are highly resistant to proteolysis, and are highly amendable to chemical diversification. However, new biological activities and folding properties of gamma-AApeptides still need to be explored. In order to expand the potential of gamma-AApeptides in chemical biology and medicinal chemistry, I have been focusing on the development of new methods to synthesize linear and cyclic gamma-AApeptides, development of one-bead-one-compound (OBOC) gamma-AApeptide libraries for the discovery of inhibitors against beta-amyloid aggregation, exploring new helical foldamers for the rational design of protein-protein interaction (PPI) inhibitors, and studying cyclic gamma-AApeptides for antimicrobial development.

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In recent years a significant research focus has been on the development of biomimicking three-dimensional substrates for cell culturing. Hydrogels mimicking the extracellular matrix is a well-suited scaffold for this purpose and there are many different ways these can be cross-linked to retain their shape. The group of Molecular Materials at IFM, Linköping University, is focusing on the development of physical hydrogels hybridized through peptide-peptide interactions but all peptides used for this today are created using rational design and on top of this very large, making them time-consuming and expensive to fabricate. The aim of this project was to evaluate if One Bead One Compound (OBOC) libraries could be used as an alternative to rational design in the finding of cyclic peptide binding partners used in the hybridization of hydrogels. The results were not very promising though since only seven peptides passed all screening steps and of these only two could be sequenced. Of these two, only one was water soluble enough to enable binding interactions analysis but was then found to be a false hit. Nevertheless, it should be noticed that only a fraction of all possible combinations was screened and the results cannot exclude OBOC libraries as an approach in the quest of finding new cyclic peptide binding partners.