Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models

Abstract

Pain is a major symptom of many diseases and results in enormous pressures on human body or society. Currently, clinically used analgesic drugs, including opioids and nonsteroidal anti-inflammatory drugs, have adverse reactions, and thus, the development of new types of analgesic drug candidates is urgently needed. Animal venom peptides have proven to have potential as new types of analgesic medicine. In this research, we describe the isolation and characterization of an analgesic peptide from the crude venom of centipede, Scolopendra subspinipes mutilans. The amino acid sequence of this peptide was identical with SsmTX-I that was previously reported as a specific Kv2.1 ion channel blocker. Our results revealed that SsmTX-I was produced by posttranslational processing of a 73-residue prepropeptide. The intramolecular disulfide bridge motifs of SsmTX-I was Cys1-Cys3 and Cys2-Cys4. Functional assay revealed that SsmTX-I showed potential analgesic activities in formalin-induced paw licking, thermal pain, and acetic acid-induced abdominal writhing mice models. Our research provides the first report of cDNA sequences, disulfide motif, successful synthesis, and analgesic potential of SsmTX-I for the development of pain-killing drugs. It indicates that centipede peptide toxins could be a treasure trove for the search of novel analgesic drug candidates. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Scolopendra subspinipes mutilans L. Koch Ameliorates Rheumatic Heart Disease by Affecting Relative Percentages of CD4+CD25+FoxP3 Treg and CD4+IL17 T Cells

“…Relative percentages of CD4 + CD25 + Tregs and CD4 + CD25 + FoxP3 Treg cells in PBMCs in the SG group were higher than in the CG group (Figure 2, P<0.05). SSLK has antibacterial [31], anticoagulant [32], and anti-inflammatory [33] properties. SSLK intervention may improve CHD symptoms of the patients by increasing the percentage of CD4 + CD25 + FoxP3 Treg cells and reducing the percentage of CD4 + IL-17 cells in PBMCs and maintained their balance (Figure 6).…”

OM‐LV20, a novel peptide from odorous frog skin, accelerates wound healing in vitro and in vivo

“…The most common typical enzyme cleavage sites are composed of “Lys‐Arg” . The 2 Da difference in the TMM (1968.49 Da) and OMW (1966.39 Da) indicated the existence of an intramolecular disulfide bridge located at the C‐terminus, which was confirmed by the OMM (1968.20 Da) of reduced native OM‐LV20 (Figure b,c).…”

Centipede Venom Peptides Acting on Ion Channels

“…Among nine K + subtypes expressed in human embryonic kidney 293 cells, SsmTx-I selectively blocked the K v 2.1 current with an IC 50 value of 41.7 nM [47]. In vivo, SsmTx-I showed potential analgesic activities in formalin-induced paw licking, thermal pain, and acetic acid-induced abdominal writhing mouse models [48].…”

“…SsmTx-1, a 36-amino-acid peptide with a mass of 4114.068 Da (Figure 7), was first isolated from the venom of Scolopendra subspinipes mutilans [47] and contains two disulfide bonds between C8-C19 and C13-C26 [48]. SsmTx-1 can potently and selectively block Kv channels in DRGs instead of Nav channels, with an IC 50 of 200 nM.…”