Protein aggregation is a serious problem in the production of recombinant proteins as well as in many neurodegenerative diseases. The principal investigator was the first to demonstrate the ability of cyclic polysaccharides known as cyclodextrins (CDs) to act as """"""""mini-chaperones"""""""" in protein folding. Cyclodextrins bind to polypeptide chains during the folding process. This prevents aggregation and promotes the folding of the protein to form its native structure. The nature of the complex and rapidly changing interactions between the folding protein and the cyclodextrins is unclear. The major objective of this proposal is to study if and how selective chemical modifications of cyclodextrin affect protein aggregation. Beta-cyclodextrin derivatives of various size, charge, functional groups and architecture will be synthesized. Structure-activity relationships between cyclodextrin chemistry and chaperone activity will be established. These studies should provide invaluable data towards a rational design and synthesis of a CD derivative with ideal anti-protein aggregation properties. Results from the proposed study will help understand the mechanisms of interactions of these cyclic oligosaccharides with unfolded, folding and folded polypeptide chains formed during protein folding. This information will be of benefit toward an understanding of in vitro and in vivo protein aggregation.
| Carter, Britton; Desai, Ankur; Sharma, Ajit (2007) Use of poly(vinyl alcohol)-coated capillaries for separation of amino-terminated polyamidoamine dendrimers. Electrophoresis 28:335-40 |
| Desai, A; Lee, C; Sharma, L et al. (2006) Lysozyme refolding with cyclodextrins: structure-activity relationship. Biochimie 88:1435-45 |
| Sharma, A; Rao, M; Miller, R et al. (2005) Fluorometric assay for detection and quantitation of polyamidoamine dendrimers. Anal Biochem 344:70-5 |
| Sharma, Ajit; Mohanty, Dillip K; Desai, Ankur et al. (2003) A simple polyacrylamide gel electrophoresis procedure for separation of polyamidoamine dendrimers. Electrophoresis 24:2733-9 |
