Nicotinic acetylcholine receptors(nAChRs) play important roles in intercellular communications of nerve cells. α-Bungarotoxins(αBtx) is a moderator for the nAChRs. Chemical synthesis provides a promising way to acce...Nicotinic acetylcholine receptors(nAChRs) play important roles in intercellular communications of nerve cells. α-Bungarotoxins(αBtx) is a moderator for the nAChRs. Chemical synthesis provides a promising way to access aBtx and their analogues. Here, we reported a new method for a-bungarotoxin by combining Fmoc-SPPS and peptide hydrazide based ligation strategy. The two-segment ligation method may enable efficient synthesis of aBtx analogues. These synthetic toxin peptides are useful tools for development of imaging or therapeutic reagents.展开更多
Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodi...Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodies,have been explored.While prophylactic vaccines are desirable,it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins.To address this,we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles.A genetically modified cell line with constitutive overexpression of theα7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind toα-bungarotoxin,a model neurotoxin.This abrogates the biological activity of the toxin,enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system.When co-administered with an immunological adjuvant,a strong humoral response againstα-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin.Overall,this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.展开更多
The snake neurotvoxins which selectively block the release of acetylcholine (ACh) from motor nerve terminals, i. e. β-type snake neurotoxins, have been proved to be a very useful tool for analysing the mechanism of t...The snake neurotvoxins which selectively block the release of acetylcholine (ACh) from motor nerve terminals, i. e. β-type snake neurotoxins, have been proved to be a very useful tool for analysing the mechanism of transmitter release. Among the β-neurotoxins β-bungarotoxin (β-BuTX) is extensively studied and widely used. β-BuTX with a展开更多
β-bungarotoxin (β-BuTX), a basic protein isolated from venom of the snake Bungarusmulticinctus, consists of two polypeptide subunits. As other snake β-neurotoxins, β-BuTXselectively inhibits release of the neurotr...β-bungarotoxin (β-BuTX), a basic protein isolated from venom of the snake Bungarusmulticinctus, consists of two polypeptide subunits. As other snake β-neurotoxins, β-BuTXselectively inhibits release of the neurotransmitter, acetylcholine, at the neuromuscular junc-tion. In the central nervous system, however, β-BuTX is cytotoxic for both展开更多
基金supported by the Science and Technological Fund of Anhui Province for Outstanding Youth(No. 1808085J04)the Innovative Program Development Foundation Hefei Center Physical Science Technology(No. 2017FXCX002)
文摘Nicotinic acetylcholine receptors(nAChRs) play important roles in intercellular communications of nerve cells. α-Bungarotoxins(αBtx) is a moderator for the nAChRs. Chemical synthesis provides a promising way to access aBtx and their analogues. Here, we reported a new method for a-bungarotoxin by combining Fmoc-SPPS and peptide hydrazide based ligation strategy. The two-segment ligation method may enable efficient synthesis of aBtx analogues. These synthetic toxin peptides are useful tools for development of imaging or therapeutic reagents.
基金supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense under award number HDTRA1-21-1-0010the National Institutes of Health under Award Numbers R21AI159492 and R21AI175904.
文摘Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodies,have been explored.While prophylactic vaccines are desirable,it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins.To address this,we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles.A genetically modified cell line with constitutive overexpression of theα7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind toα-bungarotoxin,a model neurotoxin.This abrogates the biological activity of the toxin,enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system.When co-administered with an immunological adjuvant,a strong humoral response againstα-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin.Overall,this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.
基金Project supported by the National "Climbing" Research Project Foundation of China.
文摘The snake neurotvoxins which selectively block the release of acetylcholine (ACh) from motor nerve terminals, i. e. β-type snake neurotoxins, have been proved to be a very useful tool for analysing the mechanism of transmitter release. Among the β-neurotoxins β-bungarotoxin (β-BuTX) is extensively studied and widely used. β-BuTX with a
基金Project supported by the National "Climbing" Research Project Foundation of China.
文摘β-bungarotoxin (β-BuTX), a basic protein isolated from venom of the snake Bungarusmulticinctus, consists of two polypeptide subunits. As other snake β-neurotoxins, β-BuTXselectively inhibits release of the neurotransmitter, acetylcholine, at the neuromuscular junc-tion. In the central nervous system, however, β-BuTX is cytotoxic for both
