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ENZYME INHIBITION IN THE TREATMENT OF

AIDS

By

Michael Cochran-Boucher

University of Manchester, 2010

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The Lessons of Cancer Chemotherapy

HIV has four distinct stages targeted by specific chemotherapy Attachment to CD4 Receptor Un-coating viral nucleic acid Cellular multiplication by

now integrated provirus Assembly and LIBERATION

of the Progeny

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“The Key Strategy in the treatment of AIDS has been to inhibit activity of key enzymes.”

www.informahealthcare.com

HIV Protease

Reverse Transcriptase

Integrace

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HIV Protease (Nelfinivir)• HIV Protease is an important target enzyme due to the fact that

it is the main protein responsible continued infection.

• Early X-Chrystalography provided detail of the proteins active site, giving researchers a clear target.

• Inhibition of the active site has been a main focus of drug companies and many successful drugs are currently in use. (Biochemisty by Campell & Ferell, 2008)

Image:

Center for Computaional Research, 2010.

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HIV Reverse Transcriptase (AZT) Immunogenetic HIV assays have been used to find mutations in the

genes of HIV reverse transcriptase.

Researchers have tracked mutations to specific codons.

Today, each of the codons studied have been shown to confer resistance to the various novel analogs of these now traditional treatments: Zidovudine (AZT), Lamivudine (3TC), Didanosine (ddl) and Zalcitabine (ddC)

(U.S. National Institute of health, 2008)

The HIV enzyme reverse transcriptase converts the HIV RNA into HIV DNA for integrationinto a host cell genome. Howard Hughes Medical Institute, 2009.

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HIV Integrace (Raltegravir &

MK-2048)• One of the most recent enzymes to be identified and worked with is HIV

Integrace.

• This enzyme is critical for HIV to copy and subsequently work its way inside the host ‘s cellular defences.

(Biochemisty by Campell & Ferell, 2008)

Raltegravir was approved for useOctober 12, 2007

BYU, Chemistry Department, 2010.

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Wikipedia's Version of HIV- Protease as a “British Bulldog”!

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References: Image References: www.informahealthcare.com Center for Computaional Research, 2010 BYU, Chemistry Department, 2010 Howard Hughes Medical Institute, 2009

Text References: www.informahealthcare.com Biochemistry by Campell & Ferell, 2008 U.S. National Institute of health, 2008Strategies in the Treatment of AIDs and Related Diseases: The Lessons of Cancer Chemotherapy: New Drugs. 1992, Vol. 10. 2