Pharmaceutical drugs are known for their predictable results. They achieve their constancy because they are solitary agents that bind only with specific receptors. But two agents or drugs together can cause effects other than what they produce separately.
Receptors contain small staging areas that are used by drugs, hormones and neurotransmitters for binding.These are the sites, spread throughout the body, that regulate all activity. This is the proverbial key that opens up the door to understanding life.
The molecular lock and key method to drug discovery involves the painfully slow process of trial and error. Time is needed to get the right fit so that the drug can bind with the target receptor and block or stimulate the cascade.
This all changed with the invention of combinatorial chemistry.
Combinatorial chemistry is a paradigm shift in drug discovery. It was invented in order to follow a more predictable route to ligand discovery. It utilizes a library or collection of all possible combinations of similarly structured molecular compounds.
Combinatorial chemistry is based on a finite universe of molecular possibilities. Combinatorial chemistry, as originally conceived by its inventor, Dr. George Pieczenik, utilized a library of viruses containing small peptide chains and specific sequences of nucleic acids as part of it DNA.
Each viron particle contains one sequence of amino acids, which is located on the outer envelope of the virus with the corresponding DNA that codes for it on the inside.
Combinatorial libraries are artificially created universes of molecules. Each library contains all of the finite possibilities for the given combination of compounds.
In the case of receptors and their binding domains, these libraries become clones of the active sites of receptors. These clones are then used to test various ligands for biological mimicry.
Because of the huge numbers involved, synthetic combinatorial libraries can only contain a sampling of all the possibilities. Elegant algorithms and multiple libraries are needed to reproduce the full spectrum of agents.
Once a solitary compound is discovered that can mimic, block or in any way alter the receptor’s binding, a drug is born.
Combinatorial technology is a very powerful tool that led to the development of new lead compounds that can bind to targeted receptors.
The use of computers has accelerated the development of combinatorial chemistry by automating all of the chemical reactions. Libraries can now be created that contain every volume or permutation in the series. Combinatorial chemistry represents a quantum leap in recognizing patterns. It is information gathering on a massive scale. Science is attempting to replicate Nature’s libraries.
The combinatorial method mimics nature by synthesizing the universe of possibilities and then testing against it.
Within combinatorial laboratories, chance rules. All possibilities are equally possible and probable. They believe that the universe is run by a finite set of rules based on chance. Life obeys the god of math and is not the product of any intelligent design.
In the laboratory of life, the molecular combinations found in nature are not random. They are limited and directed. Nature follows its own law of molecular directed evolution.
Natural botanical libraries (plants) contain the full spectrum of compounds including all alternate versions of the active agent. This moderates the activity of botanicals.