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Total synthesis of snake toxin α-bungarotoxin and its analogues by hydrazide-based native chemical ligation

Chinese Chemical Letters 2018年第7期29卷 1139-1142页

作者： Xiao-Qi Guo Jun Liang Ying Li Yong Zhang Dongliang Huang Changlin Tian High Magnetic Field Laboratory Chinese Academy of Sciences School of Life Science University of Science and Technology of China Department of Chemistry University of Science and Technology of China

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.

关键词： Chemical synthesis Native chemical ligation Peptide hydrazide α-bungarotoxin Nicotinic acetylcholine receptors

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Nicotine and sudden infant death syndrome

Nicotine and sudden infant death syndrome

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： David MENDELOWITZ Department of Pharmacology George Washington UniversityDC 20037USA

＜正＞Maternal cigarette smoking and prenatal nicotine exposure increase the risk for sudden infant death syndrome （SIDS） by 2- to 4-fold,yet despite adverse publicity,nearly one of four pregnant women smoke tobacco in *** who succumb to SIDS typically experience a severe bradycardia that precedes or is accompanied by centrally mediated life-threatening apneas and *** the causes of the apnea and bradycardia prevalent in SIDS victims are unknown,it has been hypothesized that these fatal events are exaggerated cardiorespiratory responses to hypoxia or *** in heart rate are primarily determined by the activity of cardiac vagal neurons（CVNs） in the brainstem. Nicotinic receptors play an important role in modulating the activity of parasympathetic CVNs in the *** of neostigmine（10μM） significantly increased the holding current,amplitude,and frequency of miniature excitatory postsynaptic current（mEPSC） glutamatergic events in *** unexposed animals,the nicotine-evoked facilitation of mEPSC frequency,but not mEPSC amplitude or holding current,was blocked byα-bungarotoxin（100 nM）.Prenatal nicotine exposure significantly exaggerated and altered the types of nicotinic receptors involved in these *** prenatal nicotine-exposed animals,α-bungarotoxin only partially reduced the increase in mEPSC *** addition,in prenatal nicotine-exposed animals,the increase in holding current was partially dependent onα-7 subunit-containing nicotinic receptors,in contrast to unexposed animals in which a-bungarotoxin had no ***/hypercapnia did not elicit an increase in excitatory neurotransmission to CVNs in unexposed animals,but in animals that were exposed to nicotine in the prenatal period,hypoxia/hypercapnia recruited an excitatory neurotransmission to ***- β- erythroidine at a concentration of 100μM totally blocked the exaggerated action of CVNs induced by hypoxia/hypercapnia in animals that were expose

关键词： maternal cigarette smoking cardiac vagal neurons hypoxia/hypercapnia α-bungarotoxin dihydro-β-erythroidine

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