東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Identification and characterization ...

Lee, Deborah Jean.

Linked to FindBook

Google Book

Amazon

博客來

Identification and characterization of a type 1 human immunodeficiency virus integrase inhibitor-binding pocket.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Identification and characterization of a type 1 human immunodeficiency virus integrase inhibitor-binding pocket./
Author:	Lee, Deborah Jean.
Description:	201 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0089.
Contained By:	Dissertation Abstracts International66-01B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3160836
ISBN:	9780496942893

Identification and characterization of a type 1 human immunodeficiency virus integrase inhibitor-binding pocket.
Lee, Deborah Jean.

Identification and characterization of a type 1 human immunodeficiency virus integrase inhibitor-binding pocket. - 201 p.

Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0089.

Thesis (Ph.D.)--University of California, Irvine, 2005.

The human immunodeficiency virus (HIV), the causative agent of the acquired immune deficiency syndrome (AIDS), is a leading cause of morbidity and mortality world-wide. According to the Joint United Nations Program on HIV/AIDS (UNAIDS), by the end of 2003 over 40 million people are infected with HIV. In the developed world, drugs that inhibit viral replication through inhibition of two of the three essential retroviral enzymes, reverse transcriptase and protease, have prolonged life in HIV-infected patients. The emergence of drug-resistant viruses has necessitated the continued discovery of new inhibitors acting on new targets. One such target is integrase (IN), a third essential retroviral enzyme.

ISBN: 9780496942893Subjects--Topical Terms:

1017734
Biology, Microbiology.

Identification and characterization of a type 1 human immunodeficiency virus integrase inhibitor-binding pocket.
LDR:03303nmm 2200277 4500 001 1823855
005 20061128084355.5
008 130610s2005 eng d
020 $a 9780496942893
035 $a (UnM)AAI3160836
035 $a AAI3160836
040 $a UnM $c UnM
100 1 $a Lee, Deborah Jean. $3 1912950
245 1 0 $a Identification and characterization of a type 1 human immunodeficiency virus integrase inhibitor-binding pocket.
300 $a 201 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0089.
500 $a Chair: W. Edward Robinson, Jr.
502 $a Thesis (Ph.D.)--University of California, Irvine, 2005.
520 $a The human immunodeficiency virus (HIV), the causative agent of the acquired immune deficiency syndrome (AIDS), is a leading cause of morbidity and mortality world-wide. According to the Joint United Nations Program on HIV/AIDS (UNAIDS), by the end of 2003 over 40 million people are infected with HIV. In the developed world, drugs that inhibit viral replication through inhibition of two of the three essential retroviral enzymes, reverse transcriptase and protease, have prolonged life in HIV-infected patients. The emergence of drug-resistant viruses has necessitated the continued discovery of new inhibitors acting on new targets. One such target is integrase (IN), a third essential retroviral enzyme.
520 $a Two of the more potent IN inhibitors described to date are L-chicoric acid (L-CA), a dicaffeoyltartaric acid (DCTA), and L-731,988, a diketoacid. Work presented herein further elucidates the in vivo mechanism of action of L-CA. Furthermore, both L-CA and L-731,988 are active against multiple clinical isolates of HIV-1. Using these compounds as lead molecules, a series of analogs were evaluated for anti-HIV and anti-IN activities. Several analogs were found to have inhibitory activities at non-toxic concentrations, though none was more potent than L-CA or L-731,988. In order to understand the specific amino acid contacts required for inhibition by L-CA and L-731,988, biochemical and virologic studies were performed using mutant IN proteins and both L-CA and L-731,988. Results from these studies have determined replication of virus in the presence of each inhibitor results in resistance to that inhibitor. Moreover, resistance to one class of inhibitor confers cross-resistance to the other class of inhibitor. Previous molecular modeling studies had identified a putative inhibitor-binding pocket on IN. Using site-directed mutagenesis, the inhibitor-binding pocket on IN was confirmed for L-CA and L-731,988. The two molecules appear to share a common binding pocket as IN mutations confer resistance to both classes of molecules. However, differences were noted with L-CA more completely filling the binding pocket and L-731,988 filling a portion of the pocket. This work identifying a common inhibitor-binding pocket on HIV IN provides an important foundation for the continued search for more potent and clinically-useful IN inhibitors.
590 $a School code: 0030.
650 4 $a Biology, Microbiology. $3 1017734
690 $a 0410
710 2 0 $a University of California, Irvine. $3 705821
773 0 $t Dissertation Abstracts International $g 66-01B.
790 1 0 $a Robinson, W. Edward, Jr., $e advisor
790 $a 0030
791 $a Ph.D.
792 $a 2005
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3160836