Method for identifying HIV-inhibiting lead compounds

This technology is a method for the identification of lead compounds for inhibition of the gp120-CD4 interaction that can be used to disrupt the uptake of HIV.

Unmet Need: Identification of HIV uptake inhibitors

The interaction between HIV gp120 glycoproteins and the immune system’s CD4 receptor is an essential step in the uptake of HIV. Due to gp120’s high mutation rate, high-throughput screens for lead compounds have not been successful. Thus, a need exists to develop techniques for identifying compounds with the desired inhibitory effect at gp120.

The Technology: Method for identifying HIV-inhibiting lead compounds

This technology is a method for the identification of inhibitors of the gp120-CD4 interaction. Although gp120 has high mutation rates, there is a highly-conserved region within the CD4 binding pocket that represents an ideal target for the development of inhibitors. This approach utilizes a library of modified CD4 constructs comprising gp120-binding epitopes and reactive residues, allowing for high-affinity binding to gp120. The gp120-CD4 complexes can be crystallized and used as structural models for designing and screening HIV-uptake inhibitors.

This technology has been validated by testing a library of 81 chemically modified CD4 constructs for their ability to inhibit the gp120-CD4 interaction.

Applications:

• Identification of compounds that inhibit the gp120-CD4 interaction
• Research tool for studying the gp120-CD4 interaction
• CD4-bound gp120 conformers for therapeutic antibody generation

Advantages:

• Improves the likelihood of identifying HIV uptake inhibitors
• Suitable for screening high affinity compounds
• Can be generalized for the identification of protein-protein interaction inhibitors

Lead Inventor:

Wayne A. Hendrickson, Ph.D.

Patent Information:

Patent Status

Related Publications:

• Xie H, Ng D, Savinov SN, Dey B, Kwong PD, Wyatt R, Smith AB 3rd, Hendrickson WA. “Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus” J Med Chem. 2007 Oct 4; 50(20): 4898-4908.

Tech Ventures Reference:

• IR 1914

• Licensing Contact: Jerry Kokoshka