One-bead-one-compound peptide libraries are powerful tools to select high affinity binders. This combinatorial methodology proved to be valuable for identifying peptides that show specific interactions with drugs, enabling the design of tailored drug solubilizers or transporters to improve pharmacological indices.[1-3] However, the selection of positive hits from the peptide libraries remains tedious as it occurs by handpicking, strongly limiting the pool of investigated beads.
Here we report our recent results on improving the analytical platform, using automated fluorescence scanning and MALDI-ToF-ToF MS/MS imaging to screen larger sets of beads, broadening the statistical base and unraveling more precisely suitable peptides. Due to permanent immobilization of the peptide libraries on a solid support during the screening process, insertion of additional washing steps is possible, creating a multi-level screening procedure. Various small molecule drugs such as photosensitizer or potential anti-Alzheimer drugs were screened for peptide interactions followed by screening for triggered release against bovine serum albumin. Thereby, strong peptide binder with unique drug release properties were identified. Furthermore, drug release from drug-transporter-complexes was investigated employing various analytical methods including fluorescence measurements and cell tests. The anti-Alzheimer drug-transporter-complexes showed e.g. positive effects on the inhibition of Tau aggregation in inducible N2a cell models, offering the replacement of traditional solubilizers by peptide-polymer conjugates.[4]
Specific peptide-polymer drug transporters were realized by choosing high affinity binder/releaser and tested for drug solubilisation and release strength, proving the applicability for potential drugs, where solubility causes currently undesired pharmacological profiles.