Synthesis and Structural Activity Relationship (SAR) of Novel Pyridazine-based Inhibitors for Inhibition of Amyloid Fibril Formation, and Biosynthesis and Optimization of L-AsparaginaseII Enzyme for Hydrolysis of Non-Native Substrate

, M.Sc. Thesis Sharif University of Technology Nazari Khodadadi, Alireza (Author) ; Kalhor, Hamid Reza (Supervisor)

Abstract

After proteins, one of the important biological macromolecules, are synthesized by ribosomes,they automatically reach their own special 3-D structure. This native structur or better known as folded state is what determines the function of a protein. In some situations, the proteins become misfolded leading to its lack of biological function through aggregation or fibril formation known as "amyloid". The amyloid fibrils have been shown to be a causative factor in nerve decay such as Alzheimer's. Therefore, inhibition of amyloid formation using different approaches such as synthetic organic and natural compounds has, recently, been under spotlight. A pyridazine basedcompound (RS-0406) has...

Cloning and Production of the Flavin Reductase Enzyme in Order to Perform Organic Reaction and Synthesis of Cation Exchange Column for Protein Purification

, M.Sc. Thesis Sharif University of Technology Hayati, Fatemeh (Author) ; Kalhor, Hamid Reza (Supervisor)

Abstract

The reductase enzymes perform an important function in the cell. These enzymes are usually coupled with other enzymes and participate in reactions such as halogenation, reduction of alkene, and carboxylic acids. These reactions are carried out by reproducing cofactors such as FADH2 and NAD+; however, there is no evidence that this enzyme alone can perform an organic reaction. In this work, we aim to examine whether recombinant flavin reductase can carry out organic reactions. In order to amplify the flavin reductase enzyme gene from the E. coli genome by PCR (Polymerase Chain Reaction) method, two synthetic primers were designed; The forward primer of the gene contained a cleavage site for...

Cloning, Expression and Purification of Yeast Fumarase Enzyme, in Order to Find Small Organic Molecules as its Allosteric Modulators

, M.Sc. Thesis Sharif University of Technology Navaee Lavasani, Elahe (Author) ; Kalhor, Hamid Reza (Supervisor)

Abstract

Enzymes are biological catalysts that carry out chemical reactions in a stereoselective manner. Fumarate hydratase (abbreviated as fumarase) is a metabolic enzyme found in both mitochondrial and cytosolic isoforms. Its mitochondrial form functions in the Krebs cycle (TCA) and specifically converts fumarate into L-malate. In recent studies, the role of the cytosolic form of this enzyme in the repair of DNA double-strand breaks has been elucidated. Fumarase and its precursors are indirectly related to many metabolic pathways, including phenylalanine and tyrosine metabolism, urea cycle, etc. As a result, it is very important to know the factors affecting this enzyme and its activity. In this...