Design and application of a peptide nucleic acid sequence targeting the p75 neurotrophin receptor.
Novel antisense peptide nucleic acid (PNA) constructs targeting p75NTR as a potential therapeutic strategy for amyotrophic lateral sclerosis (ALS) were designed, synthesised and evaluated against phosphorothioate oligonucleotide sequences (PS-ODN). An 11-mer antisense PNA directed at the initiation codon dose-dependently inhibited p75NTR expression and death signalling by nerve growth factor in Schwann cell cultures. Inhibition of p75NTR production was not detected in cultures treated with the nonsense PNA or antisense PNA directed at the 3'-terminus sequence. The 19-mer PS-ODN sequences also failed to confer any activity against p75NTR but, unlike the PNA sequences, were toxic in vitro at comparable doses.
Cheah
Irwin K
IK
School of Chemistry, Monash University, 3800, Victoria, Australia.
Cheema
Surindar S
SS
Langford
Steven J
SJ
Lopes
Elizabeth C
EC
Macfarlane
Katherine J
KJ
Petratos
Steven
S
Turner
Bradley J
BJ
D016923:Cell Death / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015195:Drug Design; D007202:Indicators and Reagents; D008970:Molecular Weight; D016472:Motor Neuron Disease / Q000188:drug therapy / Q000473:pathology; D020932:Nerve Growth Factor / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects*; D012583:Schwann Cells / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D007202:Indicators and Reagents; D016376:Oligonucleotides, Antisense; D010455:Peptides; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor