Novel surfaces derivatized with tertiary amine oxides have been prepared and tested for their ability to resist nonspecific protein adsorption. The oxidation of tertiary amines supported on triazine units was carried out using mCPBA to give a format allowing conjugation of biologically active ligands alongside them. Adsorption to these surfaces was tested and compared to adsorption to a set of commercial and custom oligo-/poly(ethylene glycol) (OEG/PEG) supports by challenging them with a protein display library presented on bacteriophage lambda. The new class of amine oxide surfaces is found to compare favorably with the performance of the OEG/PEG supports in the prevention of nonspecific binding.

Abstract. Drug reprofiling is emerging as an effective paradigm for discovery of cancer treatments. Herein, an antipsychotic drug is immobilised using the Magic Tag® chemical genomics tool and screened against a T7 bacteriophage displayed library of polypeptides from Drosophila melanogaster, as a whole genome model, to uncover an interaction with a section of 17--HSD10, a proposed prostate cancer target. A computational study and enzyme inhibition assay with full length human 17--HSD10 identifies risperidone as a drug reprofiling candidate. When formulated with rumenic acid, risperidone slows proliferation of PC3 prostate cancer cells in vitro and retards PC3 prostate cancer tumour growth in vivo in xenografts in mice, presenting an opportunity to reprofile risperidone as a cancer treatment.

We show that the use of multiple photochemistries is necessary to ensure diverse immobilisation of small molecules for binding of polypeptides using phage display and antibody libraries.

No abstract