Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0184567 (
acute pain
)
3,962
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phlotoxin-1 (PhlTx1) is a peptide previously identified in tarantula venom (
Phlogius
species) that belongs to the inhibitory cysteine-knot (ICK) toxin family. Like many ICK-based spider toxins, the synthesis of PhlTx1 appears particularly challenging, mostly for obtaining appropriate folding and concomitant suitable disulfide bridge formation. Herein, we describe a procedure for the chemical synthesis and the directed sequential disulfide bridge formation of PhlTx1 that allows for a straightforward production of this challenging peptide. We also performed extensive functional testing of PhlTx1 on 31 ion channel types and identified the voltage-gated sodium (Na
v
) channel Na
v
1.7 as the main target of this toxin. Moreover, we compared PhlTx1 activity to 10 other spider toxin activities on an automated patch-clamp system with Chinese Hamster
Ovary
(CHO) cells expressing human Na
v
1.7. Performing these analyses in reproducible conditions allowed for classification according to the potency of the best natural Na
v
1.7 peptide blockers. Finally, subsequent in vivo testing revealed that intrathecal injection of PhlTx1 reduces the response of mice to formalin in both the
acute pain
and inflammation phase without signs of neurotoxicity. PhlTx1 is thus an interesting toxin to investigate Na
v
1.7 involvement in cellular excitability and pain.
...
PMID:Chemical Synthesis, Proper Folding, Na
v
Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1. 3123 12
