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Synthesis and characterization of AibB8LysB28ProB29-insulin to study T a R conformations of insulin
Kosinová, Lucie ; Stiborová, Marie (advisor) ; Flegel, Martin (referee)
According to the International Diabetes Federation, there were 285 million people in the age from 20 to 79 years suffering from diabetes on the planet in 2010. This means diabetes has become a global epidemic so the importace of insulin research is still growing. Insulin is a protein hormone that plays a key role in regulating blood glucose level which has a widespread impact on the whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. At present, however, the active monomeric structure of insulin is still unknown. It is clear that insulin monomer must undergo structural changes upon binding to the insulin receptor as the residues crucial for the interaction are burried within the native form. According to studies of highly active hormon analogs there is an ample evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Probably, there is also great importance of the B-chain N- terminus and the transition between T and R conformation. However, the exact significance of the T and R states of insulin remains unclear. In this work, a new insulin analog AibB8LysB28ProB29-insulin was prepared for the purpose of studying significance of the T and R conformations of insulin and their relationship to the active...
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New analogues of human insulin with covalently stabilized cyclic structures in the C-terminus of the B-chain
Kaplan, Vojtěch ; Stiborová, Marie (advisor) ; Flegel, Martin (referee)
Diabetes mellitus is considered as one of world's most common metabolic diseases. Complicated treatment and increasing number of newly diagnosed patients, suffering from diabetes every year, shows the importance and necessity of research in this area. Some of the major aims of this research are the development of new therapeutically utilized drugs and defining the problems of insulin acting in human body. Insulin is a peptide hormone whose main physiological function is to regulate blood glucose level in organism connected with large impact on whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. Upon binding to the receptor molecule of insulin undergoes specific structural changes, which put the hormone into an active state. As of now, the structure of the insulin's active monomeric form is still unknown. By testing binding affinities of many modified insulin analogues there was discovered strong evidence between structural conformation of the C-terminus of the B-chain and binding affinity to the receptor. The most crucial data, necessary for this work, were observed from the structure of highly active insulin analogues that possessed unique B26 turn, recently prepared and described by team of Dr. J. Jiráček, IOCB AS CR. The aim of this work was synthesis of...
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Synthesis and characterization of AibB8LysB28ProB29-insulin to study T a R conformations of insulin
Kosinová, Lucie ; Stiborová, Marie (advisor) ; Flegel, Martin (referee)
According to the International Diabetes Federation, there were 285 million people in the age from 20 to 79 years suffering from diabetes on the planet in 2010. This means diabetes has become a global epidemic so the importace of insulin research is still growing. Insulin is a protein hormone that plays a key role in regulating blood glucose level which has a widespread impact on the whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. At present, however, the active monomeric structure of insulin is still unknown. It is clear that insulin monomer must undergo structural changes upon binding to the insulin receptor as the residues crucial for the interaction are burried within the native form. According to studies of highly active hormon analogs there is an ample evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Probably, there is also great importance of the B-chain N- terminus and the transition between T and R conformation. However, the exact significance of the T and R states of insulin remains unclear. In this work, a new insulin analog AibB8LysB28ProB29-insulin was prepared for the purpose of studying significance of the T and R conformations of insulin and their relationship to the active...
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