Dynamic combinatorial chemistry utilises reversible reactions to set up a dynamic library of molecules, with the library composition determined by the thermodynamic stability of each library member. Upon addition of a protein template, any library members which bind to the template are stabilised and amplified. Analysis of the library composition e...
Detailed herein is the tethered Biginelli condensation between irninium ion 201 and beta keto ester 206 leading to a model tricyclic ring system representative of the guanidinium core of cylindrospennopsin alkaloids. This was achieved in a biosynthetically-inspired manner in 12 steps and 8.3% overall yield from simple, commercially available 1,5-pe...
miRNAs are an important class of small non-protein coding RNAs whose specific functions in animals are rapidly being elucidated. miRNAs regulate the expression of many animal genes by post-transcriptional gene silencing and play vital roles in stem cell maintenance, differentiation and apoptosis. In this study, planarians were used as a model syste...
Amperometric enzyme electrodes have been developed for the detection of glucose, sarcosine and creatinine, and tested at "in-house" fabricated graphite rod electrodes. Determination of these analytes was primarily performed in the presence of ferrocenemonocarboxylic acid (FMCA) but also by the oxidation of enzymatically generated hydrogen peroxide ...
This thesis presents studies which investigate the application of electrospray ionisation-mass spectrometry (ESI-MS) to non-covalent protein-ligand complexes. The structural effect of desolvation on protein-ligand (P-L) complexes has been a hotly debated issue in this field and has been examined in this work. Single point mutagenesis has allowed sp...
MOSPD1 belongs to a class of proteins that have a major sperm protein (MSP) domain at the N terminus and two transmembrane domains at the C terminus and are thought to act as membrane adaptor proteins. Previous work in the laboratory indicated that the closely related, mammalian-specific, Mospd 3 plays a role in the development and function of the ...
The nuclear envelope is a complex double membrane system that separates the activities of the nuclear and cytoplasmic compartments. A recent explosion in the number of proteins associated with this subnuclear organelle together with it now being linked to over 2 dozen diseases indicates the importance of better understanding its functional organisa...
This thesis firstly describes a synthesis of the natural product taurospongin A, a potent DNA polymerase b inhibitor. Sharpless asymmetric dihydroxylation on olefin E-1.60 followed by selective deoxygenation at C(2) via Barton-McCombie reaction delivers the desired C(1)-C(10) carboxylic acid core. Subsequent esterification of the C(1)-C(10) fragmen...
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