Biochemistry, 4th Edition P49. Continuing Garrett and Grisham's innovative conceptual and organizing framework, "Essential Questions," BIOCHEMISTRY guides students through course concepts in a way that reveals the beauty and usefulness of biochemistry in the everyday world. Streamlined for increased clarity and readability, this edition also includes new photos and illustrations that show the subject matter consistently throughout the text. New end-of-chapter problems, MCAT practice questions, and the unparalleled text/media integration with the power of CengageNOW round out this exceptional package, giving you the tools you need to both master course concepts and develop critical problem-solving skills you can draw upon. | What Can Be Learned from Typical Enzyme Mechanisms 443 HUMAN BIOCHEMISTRY Protease Inhibitors Give Life to AIDS Patients Infection with HIV was once considered a death sentence but the emergence of a new family of drugs called protease inhibitors has made it possible for some AIDS patients to improve their overall health and extend their lives. These drugs are all specific inhibitors of the HIV protease. By inhibiting the protease they prevent the development of new virus particles in the cells of infected patients. A combination of drugs including a protease inhibitor together with a reverse transcriptase inhibitor like AZT can reduce the human immunodeficiency virus HIV to undetectable levels in about 40 to 50 of infected individuals. Patients who respond successfully to this combination therapy have experienced dramatic improvement in their overall health and a substantially lengthened life span. Four of the protease inhibitors approved for use in humans by the . Food and Drug Administration are shown below Crixivan by Merck Invirase by Hoffman-LaRoche Norvir by Abbott and Viracept by Agouron. These drugs were all developed from a structure-based design strategy that is the drug molecules were designed to bind tightly to the active site of the HIV-1 protease. The backbone OH-group in all these substances inserts between the two active-site carboxyl groups of the protease. In the development of an effective drug it is not sufficient merely to show that a candidate compound can cause the desired biochemical effect. It must also be demonstrated that the drug can be effectively delivered in sufficient quantities to the desired site s of action in the organism and that the drug does not cause undesirable side effects. The HIV-1 protease inhibitors shown here fulfill all of these criteria. Other drug candidates have been found that are even better inhibitors of HIV-1 protease in cell cultures but many of these fail the test of bioavailability the ability of a
