The traditional design of nucleoside reverse transcriptase inhibitors (NRTI's) involves the synthesis of chain-terminated nucleoside analogs. HIV-RT has relatively low fidelity which facilitates mutations that confer resistance towards NRTI's, also, drug promiscuity from NRTI's result in various side-effects that lead to poor patient adherence to treatment. We designed and tested two-component covalent inhibitors against HIV-RT. Our inhibitor design results in higher specificity due to its binary approach, which has previously been used in biosensing applications, where both components are necessary for therapeutic effect, and lower chances for mutagenesis because of its inhibitory action. The TCCI approach results in up to 93% inhibition of HIV-RT Furthermore, our inhibitor design is highly modular and can be adjusted towards the therapeutic targeting of other biopolymers.
Doctor of Philosophy (Ph.D.)
College of Sciences
Length of Campus-only Access
Doctoral Dissertation (Open Access)
Ledezma, Carlos, "Two-Component Covalent Inhibitors (TCCI) of the Human Immunodeficiency Virus Reverse Transcriptase (HIV-RT)" (2017). Electronic Theses and Dissertations. 5707.