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Journal of Infectious Diseases and Therapy ISSN: 2332-0877 | Volume: 6
Infectious Diseases
4
th
Annual Congress on
Neglected Tropical & Infectious Diseases
5
th
International Conference on
August 29-30, 2018 | Boston, USA
&
Probing CD4-HIV-1 gp120 Glycoprotein Interaction
Xiaobo Yu, Poulami Talukder, Zhongjie Wang, Chandrabali Bhattacharya, Nour Eddine Fahmi, Jamie A Lines, Larisa M Dedkova, Joshua LaBaer, Sidney
M Hecht
and
Shengxi Chen
Arizona State University, USA
C
D4-gp120 interaction is the first step for HIV-1 entry into host cells. A highly conserved pocket in gp120 protein is an
attractive target for developing gp120 inhibitors or novel HIV detection tools. Here we incorporate seven phenylalanine
derivatives having different sizes and steric conformations into position 43 of domain 1 of CD4 (mD1.2) to explore the
architecture of the ‘Phe43 cavity’ of HIV-1 gp120. The results show that the conserved hydrophobic pocket in gp120 tolerates
a hydrophobic side chain of residue 43 of CD protein, which is 12.2 Å in length and 8.0 Å in width. This result provides useful
information for developing novel gp120 inhibitors or new HIV detection tools. A fluorescently modified CD4 domain 1 (mD1)
protein was also designed and elaborated in an
in vitro
expression system. This fluorescent probe contains a Förster resonance
energy transfer (FRET) pair, which uses a tryptophan residue as the fluorescence donor and an acridon-2-ylalanine (Acd)
as the acceptor. When excited at 260 nm, energy was transferred from tryptophan to the Acd residue of mD1 and emitted
fluorescence at 420 nm. This fluorescence was quenched after Evans blue (EB) inhibitor or HIV-1 gp120 protein binding,
presumably as a consequence of changes in the distance and dipole orientation between the donor and acceptor; the emission
intensity at 420 nm decreased in a concentration-dependent fashion. This fluorescent CD4 probe could be developed into a
novel tool for HIV-1 gp120 protein detection. It also could be used to screen small molecules that inhibit the gp120–CD4
interaction.
Biography
Poulami Talukder has her expertise in designing and synthesizing molecules as novel treatments for infectious diseases. As a graduate student at Biodesign
Institute at Arizona State University, she successfully synthesized structurally optimized phenylalanine derivatives for incorporation into human CD4 protein to
increase the binding affinity to HIV gp120 protein which provides useful information for developing novel gp120 inhibitors. She had also worked on developing
a fluorescent CD4 probe as new HIV detection tool. While working as a postdoctoral fellow at UCSF School of Pharmacy she developed novel strategies for
increasing the efficacy of known antibiotics against the gram-negative bacteria. She also worked on structure-activity relationship (SAR) of the antimalarial ozonides
artefenomel (OZ439) and arterolane (OZ277) to improve their efficacies and ADME properties.
ptalukde@asu.eduXiaobo Yu et al., J Infect Dis Ther 2018, Volume 6
DOI: 10.4172/2332-0877-C3-045