51社区黑料

Abstract

Transition state analysis technique is a method used to study the high-energy states that molecules pass through during a chemical reaction. In drug discovery, this technique is particularly valuable because it provides insights into the precise molecular changes and energy barriers associated with enzyme-substrate interactions. Understanding the transition state greatly facilitate design inhibitors or drugs that mimic this state, leading to more effective and targeted therapies.

This talk will highlight recent progress with three enzymes that targets cancer (DNPH1), a bacterial toxin (Clostridium difficile) and a rare neurodegenerative disorder (Krabbe disease). Our team in collaboration with Prof. Schramm is developing inhibitors for DNPH1 (deoxynucleoside 5鈥�-monophosphate N-glycosidase鈥�1), a nucleotide鈥恠alvage enzyme whose inhibition may restore sensitivity to PARP inhibitors in drug-resistant breast cancers. We have also been working on designing antitoxins against 颁濒辞蝉迟谤颈诲颈耻尘鈥痉颈蹿蹿颈肠颈濒别 by neutralizing its toxins TcdA andTcdB; this strategy aims to treat 颁.鈥痉颈蹿蹿颈肠颈濒别 infections without using antibiotics which ultimately disturb gut microbiota or can cause additional damage to host tissue. Finally, we are investigating small molecule treatments for Krabbe disease, a fatal lysosomal storage disorder caused by autosomal recessive mutations in the GALC gene encoding for 尾-galacosylceramidase also called GALC. GALC deficiency leads to accumulation of galactosylceramide and downstream buildup of the cytotoxic lipid psychosine, resulting in rapid neuronal loss.

Biography

Farah Lamiable-Oulaidi is leading the Carbohydrate chemistry group at Ferrier Research Institute, New Zealand. Her group aims to develop innovative therapeutics for rare diseases, infectious diseases and drug-resistant cancers. Farah Lamiable-Oulaidi studied Chemistry at the University of Orl茅ans (France) and earned her PhD in Organic Chemistry at the ICOA-University of Orl茅ans, conducting research on pharmacological chaperones for the treatment of Gaucher Disease in the laboratory of Professors Olivier Martin and Philippe Compain. After a postdoc in the laboratory of Dr Martina Lahmann at Bangor University (United Kingdom), she joined the Ferrier Research Institute (New Zealand) to work with Professor Peter Tyler on the design and synthesis of enzyme transition-state analogue inhibitors. Dr Lamiable-Oulaidi remains closely involved in the research programs of Professors Peter Tyler and Vern Schramm (Albert Einstein College of Medicine, New York).

Research Profile