Biochemistry - Theses
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ItemTARGETING OF STAT3 TO MITOCHONDRIA AND THE ROLE OF MITOCHONDRIAL STAT3 IN REDOX HOMEOSTASIS AND CELL CYCLE(University of Hyderabad, 2022-01-21)Mitochondria are membrane-bound organelles present in all eukaryotic cells that play a fundamental role in cellular energy production, thereby referred to as the “powerhouse of the cell,” ranging in size from 0.1 to 1 μm and are round or oval. Mitochondria are enclosed by two membranes, outer mitochondrial membrane, and inner mitochondrial membrane. These two membranes are divergent in their composition and function; they further define the two aqueous sub-compartments, Inter membrane space, and Matrix.
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ItemSustainable Biocatalytic Synthesis of (S)-β-Nitro Alcohols using a Promiscuous (R)-Selective Hydroxynitrile Lyase(University of Hyderabad, 2021-12)A chiral β-nitroalcohol possesses two versatile, functional groups, a nitro and a hydroxyl, attached to vicinal carbon centers of which either one or both are asymmetric. They are essential precursors to many synthetically useful structural motifs and pharmaceuticals. The potential to transform both the nitro and hydroxyl group in a β-nitroalcohol structure could produce a diverse range of synthetic molecules with one or more different functional groups. The nitro group can be altered to amine, carbonyl, nitrile, nitrile oxide, oxime, hydroxylamine, etc.1 Chiral vicinal amino alcohols that are key building blocks of a number of β-blockers used to cure cardiovascular diseases are synthesized by a simple reduction of the nitro group of corresponding chiral β-nitroalcohols.2 The nitro group of a β-nitroalcohol is converted to a carbonyl using Nef reaction to produce α-hydroxy carbonyl.3 It undergoes denitration where the nitro group is replaced by a hydrogen.4 Similarly, the hydroxyl group can be subjected to elimination, Ritter reaction, oxidation, acetylation, etc. Simple elimination in case of a β- nitroalcohol produces nitro alkene.5 In Ritter reaction, the hydroxyl group reacts with a nitrile under acidic conditions and converts it into corresponding N-(β-nitro)amide.6 The hydroxyl group of a β-nitroalcohol can be derivatized, i.e., acetylated to produce acetylated nitroalcohol. A few examples of different drug molecules and natural products for whom (S)-β-nitroalcohols happened to be structural components are, chelonin A7 (antimicrobial), and (S)-tembamide8 (anti-HIV), (S)-toliprolol, (S)-moprolol9, and (S)-propranolol10, (S)-norphenylephrine11 (β- adrenergic receptor blocking agents), (S)-sotalol12 (antiarrhythmic agents), and (S)- miconazole13 (antifungal) (Figure 1.1, upper).
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ItemStudying the canonical and non-canonical functions of Hsp90 in Plasmodium falciparum chromatin biology( 2021-12)Malaria is one of the most ancient and deadliest infectious diseases. It still possesses a threat to mankind as half of the world population lives in the endemic regions and are at risk of malaria. According to the WHO report, in 2020 there were 241 million cases recorded worldwide, accounting for 6,27,000 deaths (1). Malaria is prevalent in more than 100 countries and territories of Africa, south Asia, southern and central parts of America, Middle East and Oceania. The causative agent of malaria is a protozoan parasite Plasmodium. The five species responsible for the manifestation of disease in human are P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi. P. falciparum is the deadliest among all the species, also causes the cerebral malaria and is responsible for maximum number of deaths due to malaria. The transmission of disease occurs through bite of the infected female Anopheles mosquitoes. A sub population is at greater risk of succumbing to the disease which includes children under age of 5 years, pregnant women, patients with HIV and immune compromised migrants. The initial symptoms of the disease include fever, chills, headache, vomiting and diarrhoea. If not treated, severity of the disease can increase and might lead to other complications like severe anaemia, respiratory distress, multiple organ failure, seizures, coma and death. The alarming scenario is that till date, there is no potent and commercial vaccine available and the emergence and spread of drug resistance in the parasites.
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ItemMOLECULAR GENETIC ANALYSIS OF LATTICE AND GRANULAR CORNEAL PYSTROPHIES IN IN'DIAN PATIENTS(University of Hyderabad, 2008-09)The cornea is a clear tissue pres,el1t at the front of the eye as shown in Figure 1.1. It provides 85% of the refractive power of the eye. It is approximately half a millimeter (550 microns) thick and has a diameter of 12 mm. The adultlilwmal1 cornea measures 11 to 12 mm horizontally and 9 to 11 mm vertically. The thickness of the cornea increases from center to periphery where it is about 0.7 mm thick. It is made up of tissue similar to that of the sclera but it has 110 blood vessels. Absence of blood vessels and orderly ar.raRgerTJent of collagel1 fibers are responsible for cormeal transparemcy. The mean diameter of collagen fibers and the mean distamce between the collagen fibers are less than half of tl7le wavelength of visible light (400-700 nm). Due to tmis orderly arramgemel1t, the scattering of incident light by one collagen fiber is canceled by the interference from the other which allows light to pass tmrough the cornea. The cornea consists of 3 main and 2 auxiliary layers as shown in Figwre 1.2. The rnainlayers from the surface to the inner eye are epithelium, stroma and endotmelium. Bowman's membrane lies between the epithelium and tl7le stroma and the Descemet's membrane is between the stroma aRd the endotmelium.
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ItemStudying the canonical and non-canonical funcations of Hsp90 in plasmodium falciparum chromatin biology(University of Hyderabad, 2021-12-21)