Category Archives: Chemical Biology

In a follow-up to our post introducing ELISA, we wanted to discuss a common application of this technique: small molecule inhibitor screening. The set up is relatively simple (1) Coat a 96-well plate with your two proteins of interest and and a detector antibody (2) add a library of 96 molecules per plate (3) Inspect which molecules inhibit the protein-protein interaction (resulting in a color loss).

Once you have have narrowed down your library to a list of inhibitors, you can rank those inhibitors by their potency/IC₅₀ by running dilution series with the exact same plate set-up:

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Where synthetic chemistry has given us many molecules that bind (and inhibit) many different proteins, chemical biology endeavors to “attach” new function to these “classical” drugs. Examples of chemical biological applications include: (1) attaching toxins or imaging agents for targeted deliver or (2) using multivalency to improve a drug’s potency. Unfortunately in order to “attach” new function to a drug you need to use a “linker” which is long and inert so it doesn’t interfer with “binding” or the new “function”. The most common linker material used in chemical biology and pharmacology is polyethylene glycol or PEG (pictured above) which is both long and inert but still impacts the properties of the drugs it is attached to(see figure above):

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In a follow-up to our introduction to fluorescence, we wanted to discuss why fluorescent probes have proven so useful in chemistry and biology. One of the main reasons is that, unlike most spectroscopic techniques which rely on a loss-of-signal or light-absorption, fluorescence is a “gain of signal” technique. As a result, the near-zero baseline/background translates into a very high signal to noise ratio for fluorescent probes. Indeed fluorescent probes have some of the greatest sensitivities of all sensors (radiation is better but has other draw backs)!

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