Prevention of HIV-1 infection and preservation of CD4 function by the binding of CPFs to gp120.
Infection by human immunodeficiency virus type-1 (HIV-1) is initiated when its envelope protein, gp120, binds to its receptor, the cell surface glycoprotein CD4. Small molecules, termed N-carbomethoxycarbonyl-prolyl-phenylalanyl benzyl esters (CPFs), blocked this binding. CPFs interacted with gp120 and did not interfere with the binding of CD4 to class II major histocompatibility complex molecules. One CPF isomer, CPF(DD), preserved CD4-dependent T cell function while inhibiting HIV-1 infection of H9 tumor cells and human T cells. Although the production of viral proteins in infected T cells is unaltered by CPF(DD), this compound prevents the spread of infection in an in vitro model system.
Finberg
R W
RW
Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115.
Diamond
D C
DC
Mitchell
D B
DB
Rosenstein
Y
Y
Soman
G
G
Norman
T C
TC
Schreiber
S L
SL
Burakoff
S J
SJ
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D005802:Genes, MHC Class II; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D013601:T-Lymphocytes / Q000276:immunology
D000998:Antiviral Agents; D001593:Benzyl Compounds; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120