A photoimmobilisation strategy that maximises exploration of chemical space in small molecule affinity selection and target discovery

Abstract

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.

A chemical genomics approach to drug reprofiling in oncology: Antipsychotic drug risperidone as a potential adenocarcinoma treatment

“…Elimination of 11 clones that also occurred in the negative control wells (no drug added) left 35 clones of interest. These were submitted to a selective elution experiment, as we have described previously [6,7] with a solution of free chlorpromazine. Significant elution in this experiment should indicate that a clone binds to unmodified drug as well as to a surface-modified analogue.…”

“…Our Magic Tag® chemical genomics tool was designed to link the known biological activity of an organic chemical with the genome as expressed through a phage displayed library of polypeptides [6,7]. Herein we demonstrate that Magic Tag® has the potential to be a new and complementary method for systematically screening known drugs to identify reprofiling opportunities.…”

Challenges and solutions for personalizing medicines

“…The use of libraries of phage molecules created from expressed ribonucleic acids allows side-by-side screening of millions of biologically relevant proteins, with rapid amplification of hits (interactions of interest). Concomitant use of new chemical immobilization tools [37] allows the effective exploration of 'chemical space' to be more efficiently compressed ( Figure 2). As an example, one such photo-immobilization approach, coupled to use of a viral library to express tissue proteins, has identified potential new off-target interactions of the common anti-asthma drug salbutamol with activation transcription factor 4, a master regulator for stress response genes ( [38]; Figure 3).…”

Advances in Parallel Screening of Drug Candidates

“…The Photoimmobilization strategy was also used to prepare small-molecules arrays onto 96-well plates [111]. The endogenous plant hormone S-(+)-abscisic acid was immobilized onto the plates by means of five different nitrene, carbene and diradical precursors and then screened against genes of Arabidopsis thaliana.…”