One Bead One Compound Screening for Cyclic Peptide Binding Partners

Abstract: 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.