Question

• Understanding the interaction between a protein and its ligand at a molecular level is important in drug design. Based on your understanding of chemical specificity, do you think drugs should be designed to be highly specific to the target site or less specific? Think about side effects and the fact that mutations (resulting in changes in protein composition) are often present – discuss advantages and disadvantages of a drug that is highly specific to its target?

Answer 1

A drug is a chemical or biochemical used in treatment (eg: malaria), prevention (eg: polio), diagnosis( eg: barium sulphate) or managment (eg: diabetes mellitus, hypertension) of a disease or disorder. Drugs intreact with blood protein as well as tissue proteins. This phenomenon is termed as protein binding.

• Once a drug is protein bound, it is unable to demonstrate its therapeutic effect. This is so because the protein bound brug is unable to bind target (receptor or enzyme).
• A drug which bind with high specificity at its target demonstrates significant pharmacological activity. This so because the receptor or enzyme is fully modulated by the drug.
• A highly bound drug may also have some secondary effects apart from pharmacological efects which may produce adverse reactions in some persons (eg: indomethacin-gastric ulcers).
• Geenerally, drugs donot cause mutation (except some which are not very frequently used; eg: alkylating agents-antoicancer activity). However, metabolites of some drugs(eg: acetaminophen) bind covalently with amino acid residue of proteins present in hepatocytes and cause necrosis.

Therefore, while designing a drug, efforts must be made to increase its specificity, with least adverse effects.

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