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Two-Component Covalent Inhibitors (TCCI) of the Human Immunodeficiency Virus Reverse Transcriptase (HIV-RT)

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Date Issued:
2017
Abstract/Description:
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.
Title: Two-Component Covalent Inhibitors (TCCI) of the Human Immunodeficiency Virus Reverse Transcriptase (HIV-RT).
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Name(s): Ledezma, Carlos, Author
Kolpashchikov, Dmitry, Committee Chair
Yestrebsky, Cherie, Committee Member
Hernandez, Florencio, Committee Member
Zhai, Lei, Committee Member
Tatulian, Suren, Committee Member
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2017
Publisher: University of Central Florida
Language(s): English
Abstract/Description: 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.
Identifier: CFE0006893 (IID), ucf:51712 (fedora)
Note(s): 2017-12-01
Ph.D.
Sciences, Chemistry
Doctoral
This record was generated from author submitted information.
Subject(s): NRTI -- HIV-RT -- Covalent Inhibition -- TCCI
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFE0006893
Restrictions on Access: public 2017-12-15
Host Institution: UCF

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