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Peptide t sequences prevent neuronal cell death produced by the envelope protein (gp 120) of the human immunodeficiency virus
Author(s) -
Brenneman Douglas E.,
Buzy Jeanine M.,
Ruff Michael R.,
Pert Candace B.
Publication year - 1988
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430150403
Subject(s) - pentapeptide repeat , peptide , biology , programmed cell death , peptide sequence , t cell , antiserum , virus , virology , immunology , antibody , microbiology and biotechnology , immune system , biochemistry , apoptosis , gene
Peptide T, an octapeptide sequence found in the external evelope protein (gp 120) of the ARV isolate of human immunodeficiency virus (HIV), was investigated for its action in preventing neuronal death observed in mouse hippocampal cultures treated with purified gp 120. Cell counts of neuronspecific enolase‐identified neurons revealed that peptide T application completely and potently antagonized gp 120‐induced death. Analogs of the core pentapeptide sequence of pepptide T, TTNYT, found in the second variable region of all gp 120 isolates sequenced to date, were also tested and found to be similarly active. Investigations of structure activity relationships of related peptides suggested that the second and fourth positions in the core pentapeptide sequence were critical for biological activity in the neuronal survival assay. Antiserum against the peptide T sequence found in the the ARV isolate was found to prevent neuronal cell death in cultures treated with purified gp 120 from the IIIB isolate of HIV. These data indicate that the peptide T sequence is effective in preventing neuronal cell death associated with the envelope protein and provide a rationale for peptide T to be evaluated as a potential therapeutic agent for the neuropsychiatric and neurological sequelae of acquired immune deficiency syndrome.