The Udugamasooriya research group is currently focusing on various types of chemical biology projects as follows:
Development of diverse peptoid libraries
This effort to incorporate diverse set of amines in to peptoid libraries as well as develop complex and higher order peptidomimetic combinatorial libraries.
OBTC cell screens to identify high specific peptoids targeting various cancer specific biomarkers
Here the peptoids are selected targeting known cancer specific receptors and proteins such as Ephs, EGFRs, VEGFRs, Fibln-5 etc.
Here the peptoids are selected targeting cancer cells over normal cells in a completely unbiased approach, which results in identification of high specific compounds that can target not only the protein biomarkers, but other molecular types such as lipids, carbohydrates etc., found on the cell surface.
Identified peptoids are validated for binding and functional activities using various in vitro biochemical tools such as ELISA, receptor phosphorylations, cell survival, toxicity etc., assays.
In vivo studies are performed through collaborations.
Development of higher order multimers of active peptoids
These projects are designed to further improve active peptoids by harnessing the ‘avidity effect’. Various types of homo-dimers, homo-trimers, homo-tetramers and other higher order multimers are designed and validated. More importantly, the hetero-dimers (formed by bringing together two different active peptoids targeting two different receptors) are validated as single compounds that can attack two signaling pathways simultaneously.
Both combinatorial and structure based design strategies are applied to develop these multimeric compounds.
Attachment of contrast agents onto active peptoids
The high specific peptoids are chemically linked with metal contrast agents such as DOTA, NOTA etc., to be used in imaging applications on MRI, PET and near-IR.
The most optimized compounds that display both therapeutic and imaging activities are developed as ‘theragnostic’ agents.
Development of on-bead combinatorial libraries of contrast agents and image at once
The versatility of peptoid chemistry is used here to modify side arms of DOTA molecules bringing wide varieties of physio-chemical properties such as charge, polarity, hydrophobicity etc. in a unique on-bead combinatorial synthesis fashion. The library imaging can be used to study how these various physio-chemical properties affect the water exchange mechanism at the metal center, ultimately allowing us to identify and develop better contrast agents for MRI, PET and other modalities.