It is hypothesized that protease inhibitors play an essential role in survival of venomous animals through protecting peptide/protein toxins from degradation by proteases in their prey or predators. However, the biological function of protease inhibitors in scorpion venoms remains unknown. In the present study, a trypsin inhibitor was purified and characterized from the venom of scorpion Mesobuthus eupeus, which enhanced the biological activities of crude venom components in mice when injected in combination with crude venom. This protease inhibitor, named Me KTT-1, belonged to Kunitz-type toxins subfamily. Native Me KTT-1 selectively inhibited trypsin with a K_i value of 130 nmol×L^(–1). Furthermore, Me KTT-1 was shown to be a thermo-stable peptide. In animal behavioral tests, Me KTT-1 prolonged the pain behavior induced by scorpion crude venom, suggesting that protease inhibitors in scorpion venom inhibited proteases and protect the functionally important peptide/protein toxins from degradation, consequently keeping them active longer. In conclusion, this was the first experimental evidence about the natural existence of serine protease inhibitor in the venom of scorpion Mesobuthus eupeus, which preserved the activity of venom components, suggests that scorpions may use protease inhibitors for survival.
Hakim MATang Xiao-Peng,YANG Shi-LongLU Qiu-MinLAI Ren
Cathelicidin Pc-CATH1 is a cathelicidin-derived myeloid antimicrobial peptide identified from Phasianus colchicus with strong antimicrobial activity against most of bacteria and fungi tested,including the clinically isolated(IS)drug-resistant strains.Considering the uniform distribution of net positive charge in both C-and N-terminus sequence of cathelicidin Pc-CATH1 and most of hydrophobic amino acid(aa)residues positioned in middle of the sequence,the antimicrobial peptide was used to investigate the structure-function relationship by truncating gradually N-or C-terminus amino acid residue.More than 10 modified peptide homo-logues(20-26 aa length)of cathelicidin Pc-CATH1 were found to keep strong antimicrobial abilities.The possible relationships between bioactivities including antimicrobial and hemolytic abilities,components of secondary structure,hydrophobicity,amphipathicity,net charge,and sequence length were investigated.The current work provided suggestions for structural and functional modification of linear,α-helical antimicrobial peptides containing no disulfided bridges.
Li DONGJuan-Juan YANGYing WANGHuan LIULi-Xian MUDong-Hai LINRen LAI
The present study was designed to search for compounds with analgesic activity from the Schizophyllum commune(SC), which is widely consumed as edible and medicinal mushroom world. Thin layer chromatography(TLC), tosilica gel column chromatography, sephadex LH 20, and reverse-phase high performance liquid chromatography(RP-HPLC) were used to isolate and purify compounds from SC. Structural analysis of the isolated compounds was based on nuclear magnetic resonance(NMR). The effects of these compounds on voltage-gated sodium(NaV) channels were evaluated using patch clamp. The analgesic activity of these compounds was tested in two types of mouse pain models induced by noxious chemicals. Five phenolic acids identified from SC extracts in the present study included vanillic acid, m-hydroxybenzoic acid, o-hydroxybenzeneacetic acid, 3-hydroxy-5-methybenzoic acid, and p-hydroxybenzoic acid. They inhibited the activity of both tetrodotoxin-resistant(TTX-r) and tetrodotoxin-sensitive(TTX-s) NaV channels. All the compounds showed low selectivity on NaV channel subtypes. After intraperitoneal injection, three compounds of these compounds exerted analgesic activity in mice. In conclusion, phenolic acids identified in SC demonstrated analgesic activity, facilitating the mechanistic studies of SC in the treatment of neurasthenia.
YAO Hui-MinWANG GanLIU Ya-PingRONG Ming-QiangSHEN Chuan-BinYAN Xiu-WenLUO Xiao-DongLAI Ren
