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The Molecular Mechanisms of ZCS for Preventing Sexual Transmission of HIV-1
Author: ZhuLin
Tutor: ChenChaoYin
School: Kunming University of Science and Technology
Course: Biochemical Engineering
Keywords: Sulfated polysaccharide SPR Interaction Drug targets Mechanism of action
CLC: R512.91
Type: Master's thesis
Year: 2009
Downloads: 4
Quote: 0
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Abstract
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ZCS is a poly anionic the esterified polysaccharide sulfate , with an average molecular weight of 24,000 . Live virus in vitro experiments show that , ZCS strongly inhibited HIV-1 replication in vitro . On this basis , in order to clarify the ZCS interaction with HIV-1 molecular mechanism , through the use of the SPR and ELISA techniques preliminary study the interaction of the ZCS with multiple potential targets . The main findings are as follows : (1) ZCS to inhibit gp120 and CD4 binding . SPR system , ZCS can significantly inhibit X4 and R5 two kinds tropism of HIV-1 gp120 and CD4 binding inhibition rates were 82.3 % ( gp120 of III B ) , and 94.3 % (gp 120ADA ) . (2) ZCS with BSA , the BSA fluorescence quenching , quenching type static quenching . ZCS stable binding with BSA complexes with BSA in accordance with the ratio of 1:1.27 . The ZCS role with BSA distance of 4.34nm. ZCS the hydrophobic force main force and BSA . (3) ZCS , with gp120 strong binding . BIAevaluation4.1 software dynamics analysis of gp120 Ⅲ B with ZCS affinity coefficient KD for 136nM ; gp120ADA with ZCS affinity coefficient KD as 442nM . ZCS with gp120 III B affinity than its affinity with gp120ADA . (4) ZCS and strong binding of the V3 variable region . Kinetic analysis by BIAevaluation 4.1 software V3 Ⅲ B with ZCS affinity coefficient KD 33.1nM ; the V3 ADA and ZCS affinity coefficient KD 20.0nM ; V3 GF - 6 ( V3 conserved sequence , GPGRAF) , with ZCS pro and coefficient KD 95.3nM. The ZCS V3 ADA affinity is greater than the V3 Ⅲ B. (5) CD4 ZCS weaker affinity . The BIAevaluation 4.1 Dynamics analysis , the CD4 and ZCS affinity coefficient 1940nM . (6) ZCS is possible to suppress the activity of the HIV-1 reverse transcriptase . The results of calculations by Graphad Prism 5 software ZCS ICso inhibition of HIV- reverse transcriptase activity to 7.437 ± 1.042μg/ml .
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CLC: > Medicine, health > Internal Medicine > Infectious disease > Viral infections > Acquired Immune Deficiency Syndrome ( AIDS AIDS)
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