Identifying compounds that modify interaction of gp120 and co-receptors, useful potentially for treating human immune deficiency virus infection, also new peptides

摘要

Identifying substances (I) that modify the interaction between the gp120 protein of human immunodeficiency virus (HIV), or its fragments, with the co-receptors CXCR4, CCR5 and/or other 7-helix transmembrane receptors for HIV, is new. Identifying substances (I) that modify the interaction between the gp120 protein of human immunodeficiency virus (HIV), or its fragments, with the co-receptors CXCR4, CCR5 and/or other 7-helix transmembrane receptors for HIV, is new. The method comprises: (a) immobilizing a ligand for the co-receptor on a gold surface; (b) contacting the ligand with suspended cells that express the co-receptor; and (c) determining interaction by measuring the refractive index (RI) by plasmon resonance. The procedure is repeated using cells that have been incubated with a test compound, and this is identified as a (I) if RI is lower for cells preincubated with it. The ligand is a linear or cyclic (glyco)peptide that includes the amino acid sequence of an HIV V3 loop (including flanking Cys). Independent claims are also included for the following: (1) similar method in which the ligand, rather than the cells, is preincubated with test compound, and active compounds are identified if there is any change (increase or decrease) in RI; (2) similar method using flow cytometry, in presence and absence of test compound, using cells as above and a fusion protein (FP) that includes the V3 loop peptide and a carrier protein (CP), then detecting binding of FP to cells using a fluorescently labeled anti-CP antibody and a reduction in the fluorescent signal indicates an inhibitor; (3) 13 7-35 residue amino acid sequences, all given in the specification; and (4) kits for the new processes.