The Prosetta Paradigm

The fundamental tenet of molecular biology is that information coded in the genetic material (DNA) is ultimately converted into proteins. Proteins come in many classes: there are structural proteins such as collagen that hold the body together, signaling proteins such as insulin that make storage and use of energy possible, and defensive proteins such as antibodies that protect the body from infection. Another extremely important class of proteins are the enzymes. Enzymes are proteins which speed up chemical reactions, a process termed catalysis. Without enzymes, life would not be possible. Each enzyme is fairly specific for a particular chemical reaction, but chemical reactions don’t occur in isolation from one another. Rather, they are organized into pathways. These are sets of chemical reactions, catalyzed by enzymes, that bring about features essential for life, such as breaking food down into components to generate chemical energy, repairing and building the components of cells and tissues of the body, and so forth.

A healthy body controls enzymes through an indirect method termed feedback. In a feedback loop, the cell is provided with “real time” information as to whether a chemical reaction needs to be sped up or slowed down, for example, by monitoring the level of the reaction’s product. These sorts of adjustments occur via “control panels” termed allosteric sites, that regulate the function of enzymes. Overall, these actions provide the balance -- termed homeostasis -- that describes the healthy condition and provides the first line of defense by the body in response to deviations from health that ultimately lead to disease.

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Most current drugs bind to the part of the enzyme directly responsible for the work the enzyme does, termed the active site. By blocking the active site, the drugs of today function as an immediate “on/off” switch for the chemical reactions whose rates are controlled by the enzyme. This approach is very blunt and very different from how the body naturally regulates the enzymes that control its chemical reactions.  Furthermore, any individual protein can, when working in concert with other proteins, perform different functions and involve itself in multiple regulatory pathways. The conventional drug discovery focus on single functions of individual proteins misses both this diversity of multi-protein complex structures in which any given protein can be found and the heterogeneity of protein function.

Prosetta drugs target the multi-protein complexes whose function is to allosterically regulate homeostasis under normal conditions.  We hypothesize that diseased states are indicators of aberrancies in the enzyme-controlled feedback loops and that facilitating a “return to normal” is the best way to cure underlying conditions. This approach allows for nuanced control over the most intricate biological processes with minimal toxic side effects.

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Using the Prosetta Paradigm and platform, we have identified small molecules with unprecedented activities against viral, bacterial, fungal, parasitic, malignant, inflammatory, and degenerative diseases. While these drugs are still early – none have yet been given to humans – their novel biological activities suggest they will expand the capabilities of biomedical science.

For a more technical description of our drug discovery platform please click here .