New biological tARGETS IN DRUG DEVELOPMENT

UNDER GUIDENCE OF GEETHA REDDY Associate professor Biotechnology department.

PRESENTED BY M.PRATHYUSHA 10T22S0109

CONTENTSDefinitionTypes of targetsMechanismEnzymesTypes of inhibitionApplications of enzymesLigand gated ion channelsRegulation & structure New biological targetsConclusion

BIOLOGICAL TARGET

A biological target is a biopolymer such as a protein or nucleic acid whose activity can be modified by an external stimulus.

The definition can refer to the biological target of a pharmacologically active drug compound, or the receptor target of a hormone(like insulin).

TYPES OF TARGETS

The most common drug targets of currently marketed drugs include:

G protein-coupled receptors (target of 50% of drugs) Enzymes (especially protein kinases) Ligand-gated ion channels Voltage-gated ion channels Nuclear hormone receptors

MECHANISM

The interaction between the substance and the target may be:

Non-covalent

Reversible covalent - A chemical reaction occurs between the stimulus and target in which the stimulus becomes chemically bonded to the target, but the reverse reaction also readily occurs in which the bond can be broken.

Irreversible covalent - The stimulus is permanently bound to the target through irreversible chemical bond formation.

Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions.

In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products.

Almost all chemical reactions in a biological cell need enzymes in order to occur at rates sufficient for life.

ENZYMES

LOCK AND KEY MODEL

TYPES OF INHIBITION

Competitive inhibition Un competitive inhibition Non-competitive inhibition Mixed inhibition

USES OF INHIBITORSSince inhibitors modulate the function of enzymes they are often used as drugs. A common example of an inhibitor that is used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin, thus suppressing pain and inflammation.

http://en.wikipedia.org/wiki/File:Competitive_inhibition.svg

BIOLOGICAL FUNCTION

Enzymes serve a wide variety of functions inside living organisms. They are indispensable for signal transduction and cell regulation, often via kinases and phosphatases.They also generate movement, with myosin hydrolysing ATP to generate muscle contraction.

Other ATPases in the cell membrane are ion pumps involved in active transport.

The importance of enzymes is the fact by lethal illness. One example is phenylketonuria.

A mutation of a single amino acid in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation of phenylalanine, results in build-up of phenylalanine and related products. This can lead to mental retardation if the disease is untreated.

INVOLVEMENT IN DISEASES

APPLICATIONS OF ENZYMES

Food processing -- Amylases from fungi & plants

Baby foods -- Trypsin

Fruit juices -- Cellulases & pectinases

Biological

detergents -- Amylases & lipases

Contact lens -- Proteases

Molecular Restriction enzymes,DNA

biology -- ligases & polymerases.

Ligand-gated ion channels (LGICs) are ionotropic receptor or channel-linked receptor.

They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger  such as a neurotransmitter .

LIGAND-GATED ION CHANNELS

REGULATION

The ion channel is regulated by a ligand and is usually very selective to one or more ions like Na+, K+, Ca2+.

Many LGICs are additionally modulated by allosteric ligands, by channel blockers, ions, or the membrane potential.

Each subunit of the pentameric channels consist of the extracellular ligand-binding domain and a transmembrane domain. Each transmembrane domain in the pentamer includes four transmembrane helixes.

Example: Nicotinic acetylcholine receptor

STRUCTURE

NEW CELLULAR TARGETS FOR HIV DRUG DEVELOPMENT

Science Daily (May 28, 2009) — Focusing HIV drug development on immune cells called macrophages instead of traditionally targeted T cells could bring us closer to eradicating the disease, according to new research from University of Florida and five other institutions.

EMERGING TARGETS FOR DIABETES

The two targets protein tyrosine phosphates 1B(PTP-1B) & Glycogen Synthase kinase-3(GSK-3) have emerged as validated targets for treating this disease.

This two targets are studied which plays a key role in insulin signalling pathway as potential targets for development of anti diabetic therapies.

High Mobility Group A1 Protein - a New Regulator for Peroxisome Proliferator Activated Receptor gamma Transcriptional Repression - Inhibits Inflammatory Gene Response in Human Aortic Smooth Muscle Cells

The project aims to identify new nuclear cofactors for PPARgamma (peroxisome proliferator-activated receptor gamma)-dependent gene transcription in human aortic smooth muscle cells (HASMC) in order to develop new PPARgamma-ligands with improved clinical safety to exert deleterious cardiovascular side effects.

New drug targets for squamous cell carcinoma

Researchers at Fred Hutchinson Cancer Research Center have discovered a new drug target for squamous cell carcinoma – the second most common form of skin cancer. Scientists have found that a protein called alpha-catenin acts as a tumor suppressor and they also have unlocked the mechanism by which this protein controls cell proliferation.

Scientists discover new drug target for inflammatory bowel disease: cytokine (IL-23).

New treatments for illnesses like Crohn's disease and ulcerative colitis are on the horizon. That's because they've identified IL-23, a cytokine used by the immune system to ward off disease, as a major contributor to the inflammation that is the hallmark of these illnesses. With this information, it is now possible to develop new treatments that stop or reduce the damaging effects of IL-23, potentially bringing relief to millions of people with inflammatory bowel disease (IBD) and possibly other inflammatory illnesses as well.

CONCLUSION

Biological targets have been vastly used in drug development process. Many R&D companies are in search of new drug targets in biological systems in order to treat various disorders. It is said to be very high demand and scope for biological targets in biotechnology industries.