DISCOVERY AND BIOPHYSICAL CHARACTERIZATION OF ALLOSTERIC INHIBITORS OF FACTOR XIa (FXIa)

Thrombosis is one of the leading causes of mortality and morbidity that is associated with myocardial infarction, stroke and pulmonary embolism. Anti-thrombotic agents which intend to reduce the occurrence and severity of thrombosis usually target the enzymes of the coagulation cascade. FXIa, a 160 kDa homodimer is gaining popularity of late as a potential target for anti-thrombotic agents due to its relative safety. A number of inhibitors which target the active site of FXIa have been reported but to our knowledge there have been no inhibitors which act via an allosteric mechanism. The aim of this project was to screen for allosteric inhibitors of FXIa from of pool of sulfated small-molecules.These molecules were primarily designed to act as heparin mimetics; heparin being a natural anti-coagulant. These compounds were then analyzed to determine whether inhibition was via an allosteric mechanism.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Pharmaceutical Sciences

Year dc:date.available

2012

Author dc:creator

• Argade, Malaika

Contributors dc:contributor

• Umesh Desai

• Factor XIa
• Medicine and Health Sciences
• Pharmacy and Pharmaceutical Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/418

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1417