Recombinant Expression in Pichia pastoris System of Three Potent Kv1.3 Channel Blockers: Vm24, Anuroctoxin, and Ts6

Recombinant Expression in Pichia pastoris System of Three Potent Kv1.3 Channel Blockers: Vm24, Anuroctoxin, and Ts6

The Kv1.3 channel has become a therapeutic target for the treatment of various diseases. Several Kv1.3 channel blockers have been characterized from scorpion venom; however, extensive studies require amounts of toxin that cannot be readily obtained directly from venoms. The Pichia pastoris expressio...

Full description

Saved in:
Bibliographic Details
Published in:Journal of fungi (Basel) Vol. 8; no. 11; p. 1215
Main Authors: Borrego, Jesús, Naseem, Muhammad Umair, Sehgal, Al Nasar Ahmed, Panda, Lipsa Rani, Shakeel, Kashmala, Gaspar, Attila, Nagy, Cynthia, Varga, Zoltan, Panyi, Gyorgy
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 17-11-2022
MDPI
Subjects:
Amino acids
Biological activity
Chemical synthesis
Cloning
E coli
Glycerol
Kv1.3 blockers
Peptides
Pichia pastoris
Potassium
Potassium channels (voltage-gated)
Proteins
recombinant peptides
scorpion venoms
Therapeutic targets
Toxins
Venom
Yeast
United States > US
scorpion venoms
Pichia pastoris
recombinant peptides
Kv1.3 blockers
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The Kv1.3 channel has become a therapeutic target for the treatment of various diseases. Several Kv1.3 channel blockers have been characterized from scorpion venom; however, extensive studies require amounts of toxin that cannot be readily obtained directly from venoms. The Pichia pastoris expression system provides a cost-effective approach to overcoming the limitations of chemical synthesis and E. coli recombinant expression. In this work, we developed an efficient system for the production of three potent Kv1.3 channel blockers from different scorpion venoms: Vm24, AnTx, and Ts6. Using the Pichia system, these toxins could be obtained in sufficient quantities (Vm24 1.6 mg/L, AnTx 46 mg/L, and Ts6 7.5 mg/L) to characterize their biological activity. A comparison was made between the activity of tagged and untagged recombinant peptides. Tagged Vm24 and untagged AnTx are nearly equivalent to native toxins in blocking Kv1.3 (Kd = 4.4 pM and Kd = 0.72 nM, respectively), whereas untagged Ts6 exhibits a 53-fold increase in Kd (Kd = 29.1 nM) as compared to the native peptide. The approach described here provides a method that can be optimized for toxin production to develop more selective and effective Kv1.3 blockers with therapeutic potential.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2309-608X
2309-608X
DOI:10.3390/jof8111215