Research in the group is in the areas of Biological, Natural Product and Synthetic Chemistry. We are interested in developing small molecules that can be used to reveal structural and functional paradigms of biological receptors, in particular those that lead to neurodegenerative disorders. Current research projects include (i) investigation of chemistry and biology of amyloid peptides, (ii) development of chemical tools for site-specific modification of proteins; and (iii) synthesis of functionally diverse compounds based on natural product scaffolds.

i). Amyloid peptides (Ab), 39-43 amino acid long peptides, are believed to be among the main pathological agents leading to the occurrence and progression of Alzheimer¦Äs disease. These peptides exhibit a complex aggregation profile, in addition to multiple interactions with various biological receptors, and lead to the formation of numerous neurotoxic species, and finally contribute to the formation of senile plagues found in the brains of Alzheimer¦Äs disease patients. The neurotoxicity of amyloid species is poorly understood, and elucidation of molecular mechanisms involving amyloid peptides holds a lot of promise for developing efficient remedies. We are pursuing the possibility of controlling the aggregation propensity of amyloid peptides by small molecule-based ’â€peptidases’â§. A complementary approach is on the design of small molecules that can detect and alter the interactions of amyloid peptides with various biological receptors.

ii) The ability to monitor protein-protein interactions has numerous important implications in chemistry, biology, engineering and medicine. Attachment of desired molecules to a protein provides a tool for elucidation of protein functionality. Currently, limited number methods that allow selective functionalization of specific amino acid residues are available. We are developing synthetic methodologies for site-specific labeling of various proteins with fluorescent, photoactive and affinity-based moieties in order to elucidate the physiological and pathological functions of these biomolecules.

iii) Natural products provide a never-ending inspiration for discovering new modes of chemical and biological reactivity and selectivity. Numerous, natural products possess suitable moieties, which enable the introduction of diverse functionalities into the molecule. Our group is engaged in developing protocols for facile and efficient isolation of biologically active and structurally interesting natural products from various herbal extracts. Subsequently, these natural products will be used as scaffolds to create compounds with a desired mode of biological action.

'A concise synthesis of ginkgolide M, a minor component of terpene trilactone fraction from Ginkgo biloba roots,’⧠S. Bolshakov, S. V. Dzyuba, J. Decatur, K. Nakanishi, J. Nat. Prod., 2006, 69, 429-431.

'Regioselective thionocarbonation of ginkgolides: facile preparation of ginkgolide J.’⧠S. V. Dzyuba, S. Bolshakov, K. Nakanishi, Tetrahedron Lett., 2005, 46, 7797-7799.

'Stereoselective oxidations and reductions catalyzed by non-redox proteins.’⧠S. V. Dzyuba, A. M. Klibanov, Tetrahedron: Asymmetry, 2004, 15, 2771-2777.

'Asymmetric thiosulfinations catalyzed by bovine serum albumin and horseradish peroxidase.’⧠S. V. Dzyuba, A. M. Klibanov, Biotechnol. Lett., 2003, 25, 1961-1965.

'Recent advances in applications of room-temperature ionic liquid/supercritical CO2 systems.’⧠S. V. Dzyuba, R. A. Bartsch, Angew. Chem. Int. Ed., 2003, 42, 148-150.

'Expanding the polarity range of ionic liquids.’⧠S. V. Dzyuba, R. A. Bartsch, Tetrahedron Lett., 2002, 43, 4657-4659.

'Influence of structural variations in room-temperature ionic liquids on the selectivity and efficiency of competitive alkali metal salt extraction by a crown ether.’⧠S. Chun, S. V. Dzyuba, R. A. Bartsch, Anal. Chem., 2001, 73, 3737-3741.