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Synthesis and characterization of new insulin analogs with a triazole bridge at the C-terminus of the B chain
Kuntová, Vendula ; Jiráček, Jiří (advisor) ; Ryšlavá, Helena (referee)
Insulin is a peptide hormone responsible for maintaining glucose homeostasis in the circulation. Insulin interacts with two isoforms of the insulin receptor, IR-A and IR-B, which have different tissue distribution. IR-A is supposed to have rather mitogenic function and IR-B rather metabolic function. The goal of this study was to develop insulin analog, which will be more selective for IR-B than human insulin. We prepared three new insulin analogs with a 1,2,3-triazole bridge at the positions B26 and B29. The triazole bridge was formed by Cu(I)- catalysed cycloaddition between side chains of azidopentanoic acid (N3Pent) at B26 and propargylglycine (Prg) at B29. The analogs differed in configurations on C carbons of unusual amino acids at the positions B26 and B29. Specifically, we prepared insulin analog 1 with D- N3PentB26 and D-PrgB29, insulin analog 2 with D-N3PentB26 and L-PrgB29 and insulin analog 3 with L-N3PentB26 and D-PrgB29. New analogs were tested for their binding to both isoforms (IR-A and IR-B) of the insulin receptor. Analogs 1 and 2 were less potent in binding than human insulin and had no selectivity for receptor isoforms. Analog 3 was 4-times more potent in binding to IR-B and 2-times more potent in binding to IR-A than human insulin. However, the binding selectivity of the...
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Effect of cytokinin deficiency on oxidative damage and antioxidant defence during ageing and abiotic stress
Mýtinová, Zuzana ; Wilhelmová, Naďa (advisor) ; Ryšlavá, Helena (referee) ; Prášil, Ilja (referee)
Conchsiom l) Leaves of Úmsgenie tobmo with refuced lwd of CK agedmme sbwly, cmtrary to the contol leaves' AtcKx2 planÉsmaintainedhigher Chl cont€nt ed protein cmtd' md alsohigherphotosyntfuticperformmoein theoldestleaves. 2) We observed elevated mtioxidmt (bott enrynalc md low-moleculr) ftnctional alreadyin theyoungestleavesof AICI(X2. 3) Enhmoementof oertaindioxidmt defencecould be cased oryenscory eff€ct of tb€ decÍeas€ in the level of Úotd CKq assumedas potedial m-ea4nnďic mtioxidmts or as a resultof oxidative súessin&rcedby thelack ďCKs in yorog deve|opingleaves. 4) It is plarrsible thaÍthe higba mtioxidant defeirce migbt comĚute to retÚdation of ageingwitt a consequ€Írc€ of postponedonsetof serrescencein lwes with a defioienoy ofCKs. 5) Tbe responsesof AoE a.tiúties to individual sresses ditreredbetweenleavesmd roots ofboth WT mdAtCKX2 torbacoofuts. ó) The higho toleranceof AICKX2 plms cotúdbe affiib}t€d to noticeably higber activity of GR in leaves md APX SOD md CAT in roots displayed aheady mder cmnol conditions. Althougb rrmsgenic tobacco plmts possess, ď l€ast prtiďy' berer ffiioxidd protection in non-stressedoonditions,they were not oonfirmed to be more tolermt to abiotic sb€ss€s. 7) The ďfference between md WT plants in theř stess Í€spons€s could be associďed with ďvergent seosfiúý to imposed...
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