HIV Infection Studies

HIV targets the T-cells, gaining entry through a cascade of events mediated by the viral gylcoproteins gp120 and gp41. Gp120 is a surface protein, noncovalently bound to the transmembrane protein gp41. Together these two glycoproteins are presented in trimeric form on the viral surface. Current chemotherapeutic intervention of HIV infection are directed toward inhibiting enzymes that are required for viral replication, once a host cell has been invaded However, the emergence of viral strains that are resistant to these drugs has fueled investigations into alternative intervention strategies. One active and promising area of research has focused on preventing HIV entry into host cells. Therefore, fundamental and molecular level understanding of the gp120 adhesion process is required in order to develop novel metholds for detecting and deacitating the HIV virals.
Our group focuses on engineering nanostructures of HIV binding ligands to mimic the Cellular membranes, and the regulation of the gp120 binding to these artificially engineered structures by changing the geometry, local environment and functionality. Approaches include (1) production of nanostructures of ligands using scanning probe lithography and advanced nanofabrication methodologies developed in Liu lab; (2) in situ and real time monitoring of gp120 binding to the engineered structures to correlate the binding behavior with the geometry, local environment and functionality of the nanostructures and (3) binding of HIV viruses with the nanostructures of ligands.
Recent progress includes: (1) successful production of nanostructures of carbohydrate ligands (Gal and GalCer) using nanografting and self-assembly; (2) immobilization of viral protein rgp120 onto Gal and GalCer terminated self-assembled monolayers (SAMs); and (3) preliminary success in adhering rgp120 to nanostructures of ligands.

HIV Infection Studies
HIV targets the T-cells, gaining entry through a cascade of events mediated by the viral gylcoproteins gp120 and gp41. Gp120 is a surface protein, noncovalently bound to the transmembrane protein gp41. Together these two glycoproteins are presented in trimeric form on the viral surface. Current chemotherapeutic intervention of HIV infection are directed toward inhibiting enzymes that are required for viral replication, once a host cell has been invaded However, the emergence of viral strains that are resistant to these drugs has fueled investigations into alternative intervention strategies. One active and promising area of research has focused on preventing HIV entry into host cells. Therefore, fundamental and molecular level understanding of the gp120 adhesion process is required in order to develop novel metholds for detecting and deacitating the HIV virals. Our group focuses on engineering nanostructures of HIV binding ligands to mimic the Cellular membranes, and the regulation of the gp120 binding to these artificially engineered structures by changing the geometry, local environment and functionality. Approaches include (1) production of nanostructures of ligands using scanning probe lithography and advanced nanofabrication methodologies developed in Liu lab; (2) in situ and real time monitoring of gp120 binding to the engineered structures to correlate the binding behavior with the geometry, local environment and functionality of the nanostructures and (3) binding of HIV viruses with the nanostructures of ligands. Recent progress includes: (1) successful production of nanostructures of carbohydrate ligands (Gal and GalCer) using nanografting and self-assembly; (2) immobilization of viral protein rgp120 onto Gal and GalCer terminated self-assembled monolayers (SAMs); and (3) preliminary success in adhering rgp120 to nanostructures of ligands.
	Figure 1. Structures of the thiolated natural ligand GalCer and its analogue Gal.
	Figure 2. Binding of protein rgp120 onto a mixed Gal/hexanethiol SAM.[A] A 1000 × 1000 nm2 topographic image showing the binding of protein on the surface. [B] Cursor profile of the line in [A].

Figure 3. Construction of ligand Gal and GalCer nanostructures by nanografting. [A] 300 × 300 nm2 AFM topographic image showing a 130 × 110 nm2 Gal pattern. [B] Cursor profile corresponding to the line in [A]. [C] Side View of a proposed packing model of the ligand Gal molecules within the pattern. [D] A 600 × 600 nm2 AFM topographic image showing eleven nanogrfted lines of ligand GalCer. [E] Cursor profile of line drawn in [D].
	Figure 4. Spatially Selective Binding of rgp120 onto a Mixed Gal/hexanethiol Nanostructure.[A] A 520 × 450 nm2 topographic image showing a hexanethiol frame nanografted surrounding a mixed Gal/hexanethiol matrix to form a isolated ligand Gal pattern. [B] Same area after rgp120 injection showing selective binding of rgp120 molecules onto the ligand Gal nanostructure.
Publications: (1). "Structures of Annealed Decanethiol Self-Assembled Monolayers on Au(111): an Ultrahigh Vacuum Scanning Tunneling Microscopy Study" Qian, Y.; Yang, G.; Yu, J. J.; Jung, T.A.; Liu,G-Y. Langmuir 2003, 19,6056-6065. (2). "Synthesis of Gold Glyconanoparticels and Biological Evaluation of Recombinant Gp120 Interactions" Notlting, B.; Yu, J. J.; Liu,G-Y.; Cho, S.-J.; Kauzlarich, S.; Gervay-Hague, J. Langmuir 2003; 19, 6465-6473.