The in vitro biological effect of nerve growth factor is inhibited by synthetic peptides.
Nerve growth factor (NGF)1 is a neurotrophic polypeptide that acts via specific receptors to promote the survival and growth of neurons. To delineate the NGF domain(s) responsible for eliciting biological activity, we synthesized small peptides corresponding to three regions in NGF that are hydrophilic and highly conserved. Several peptides from mouse NGF region 26-40 inhibited the neurite-promoting effect of NGF on sensory neurons in vitro. Inhibition was sequence-specific and could be overcome by increasing the concentration of NGF. Moreover, peptide actions were specific for NGF-mediated events in that they failed to block the neurotrophic activity of ciliary neuronotrophic factor (CNTF) or phorbol 12-myristate 13-acetate (PMA). In spite of the inhibition of NGF activity, peptides did not affect the binding of radiolabeled NGF. These studies define one region of NGF that may be required for neurotrophic activity.
Longo
F M
FM
Department of Neurology, University of California, San Francisco 94143.
Vu
T K
TK
Mobley
W C
WC
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D020934:Ciliary Neurotrophic Factor; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D013755:Tetradecanoylphorbol Acetate