Dendrimers as Size Selective Binding Reagents to Proteins

Protein-protein interaction is the key element in the biological processes. Dendrimers, owing to their unique characters such as globular size, nanoscale, mono-dispersed molecular weight distribution and.customisable functional groups may bind to proteins in a similar manner to nature, through electrostatic interaction and shape selection. PAMAM dendrimers and mesotetrakis( 4-caboxyphenyl) porphyrin (TCPP) cored polypeptide dendrimers were synthesised to study the binding affinities and interfacial areas of the proteins, such as cytochrome c and a-chymotrypsin. Carboxylate PAMAM dendrimers have been found that can inhibit the hydrolysis function 'of achymotrypsin. The complex of porphyrin and PAMAM were used as competitive binding reagents to cytochrome c. It was found that the binding strength between the protein and dendrimer was related to the interfacial area of the protein's active site and the residue charge distribution around it. Fluorescence quenching study of the TCPP cored dendrimers by the cytochrome c revealed the binding constants between them are around micromolar and varied with the size of the dendrimers. The generation 2 TCPP cored polyglutamic acid dendrimer was found to bind best to cytochrome c, in which its applicable size was matched to cytochrome c's interfacial area. This study shall hopefully give some insight into developing future macromolecular therapeutics.EThOS - Electronic Theses Online ServiceGBUnited Kingdo