ORGN 910 |
| Proteins play a crucial role in life by regulating the many complex biological processes in nature. The function of many of these proteins and the mechanism by which they operate is still unknown. Therefore, developing new protein targeting tools to study the function of biomolecules will become increasingly important in the future. Additionally, being able to selectively target proteins also means that non-natural fragments can be introduced into these biomolecules, creating many interesting new chemical/biological applications. In this paper we will present new strategies that we are developing for the selective targeting of biomolecules.[1] Various newly developed phosphonate suicide inhibitors for lipases and proteases will be presented and we will show how an active site-directed protocol can be used to covalently modify these enzymes with small diagnostic organic/organometallic fragments (Scheme). We show how these enzyme-hybrids can be studied with mass spectrometry and gel-electrophoresis in combination with UV/Vis spectroscopy. Furthermore, we have studied the kinetics of the protein inhibition events using an activity assay based on carboxylic ester hydrolysis and, in special cases, with fluorescence spectroscopy. Additionally, the in situ functionalisation of protein-N3 hybrids using a catalytic click reaction will be presented. The latter protocol is used to selectively modify the enzymes with molecular tags (e.g. biotin, fluorophores) that can be used for protein diagnosis/analysis and potentially for selective protein pull-down protocols. [1] Kruithof et al, Chem. Eur. J. 2005, 11, 6869
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Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
8:00 AM-12:00 PM, Thursday, August 23, 2007 BCEC -- 258B, Oral
Division of Organic Chemistry |
