2. New biological tARGETS INDRUG DEVELOPMENT

3. UNDER GUIDENCE OF GEETHA REDDY Associate professor Biotechnology department. PRESENTED BY M.PRATHYUSHA 10T22S0109

4. CONTENTS Definition Types of targets Mechanism Enzymes Types of inhibition Applications of enzymes Ligand gated ion channels Regulation & structure New biological targets Conclusion

5. 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 activedrug compound, or the receptor target of a hormone(like insulin).

7. Enzymes (especially protein kinases)

8. Ligand-gated ion channels

9. Voltage-gated ion channels

11. 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.

13. LOCK AND KEY MODEL

15. Un competitive inhibition

16. Non-competitive inhibition

17. Mixed inhibitionUSES OF INHIBITORS Since 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.

19. 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.

20. INVOLVEMENT IN DISEASES 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 retardationif the disease is untreated.

22. Baby foods -- Trypsin

23. Fruit juices -- Cellulases & pectinases

25. Molecular Restriction enzymes,DNA biology -- ligases & polymerases.

26. LIGAND-GATED ION CHANNELS 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.

27. 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.

28. STRUCTURE 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

29. 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.

30. 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.

32. 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.

33. 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.

34. 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.

35. 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.