A5042137574- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Synthesis and Biological Evaluation
- Chemical Synthesis and Analysis
- Neuropeptides and Animal Physiology
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Salivary Gland Disorders and Functions
- Proteoglycans and glycosaminoglycans research
- Effects of Radiation Exposure
- Esophageal Cancer Research and Treatment
- Gastrointestinal Tumor Research and Treatment
- Gastrointestinal disorders and treatments
- Mycorrhizal Fungi and Plant Interactions
- Antimicrobial Peptides and Activities
- Oral microbiology and periodontitis research
- Biochemical and Structural Characterization
- Photoreceptor and optogenetics research
- Advanced Fluorescence Microscopy Techniques
- Technology and Data Analysis
- Neurobiology and Insect Physiology Research
- Cancer Immunotherapy and Biomarkers
- Radiopharmaceutical Chemistry and Applications
Hainan University
2015-2024
Guangxi University
2020-2024
Zunyi Medical University
2024
Ministry of Education of the People's Republic of China
2018-2019
Henan Cancer Hospital
2019
University of Utah
1999-2019
Significance The α9α10 nicotinic AChR (nAChR) subtype is a recently identified target for the development of breast cancer chemotherapeutics and analgesics, particularly to treat neuropathic pain. Structure/function analyses antagonists this are therefore essential specific therapeutic compounds. Conus genus rich source pharmacologically active peptides, we report here that αO-conotoxin GeXIVA potent selective antagonist nAChR subtype. displays unique structural properties among other...
α-Conotoxins are disulfide-rich peptides that competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Despite their small size, different α-conotoxins able to discriminate among subtypes mammalian nAChRs. In this report, the activity two from venom Conus pennaceus, PnIA and PnIB, examined. Although toxins differ in only residues, preferentially blocks α3β2 nAChRs, whereas PnIB prefers α7 subtype. Point mutation chimeras these were synthesized activities assessed on Xenopus...
This study was performed to discover and characterize the first potent α3β2-subtype-selective nicotinic acetylcholine receptor (nAChR) ligand. A novel α4/7-conotoxin, α-CTxLvIA, cloned from Conus lividus. Its pharmacological profile at Xenopus laevis oocyte-expressed rat nAChR subtypes determined by 2-electrode voltage-clamp electrophysiology, its 3-dimensional (3D) structure NMR spectroscopy. α-CTx LvIA is a 16-aa C-terminallyamidated peptide with 2-disulfide bridges. Using subunits...
The α3β4 nAChRs are implicated in pain sensation the PNS and addiction to nicotine CNS. We identified an α-4/6-conotoxin (CTx) TxID from Conus textile. new toxin consists of 15 amino acid residues with two disulfide bonds. was synthesized using solid phase methods, synthetic peptide functionally tested on heterologously expressed Xenopus laevis oocytes. blocked rat a 12.5 nM IC50, which places it among most potent nAChR antagonists. also closely related α6/α3β4 94 IC50 but showed little...
α6β2 Nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic neurons in the CNS are potential therapeutic targets for treatment of several neuropsychiatric diseases, including nicotine addiction and Parkinson disease. However, recent studies indicate that α6 subunit can also associate with β4 to form α6β4 nAChRs difficult pharmacologically distinguish from α6β2, α3β4, α3β2 subtypes. The current study characterized a novel 16-amino acid α-conotoxin (α-CTx) TxIB Conus textile...
Conotoxins (CTxs) selectively target a range of ion channels and receptors, making them widely used tools for probing nervous system function. have been previously grouped into superfamilies according to signal sequence families based on their cysteine framework biological target. Here we describe the cloning characterization new conotoxin, from Conus vexillum, named αB-conotoxin VxXXIVA. The peptide does not belong any described conotoxin superfamily its arrangement Cys residues is unique...
Abstract Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties nAChRs. X-ray crystal structures AСhBP in complex with α-conotoxins provide important insights into interactions distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet solved. Here...
The α3β2 and α3β4 nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central peripheral nervous systems, playing critical roles various physiological processes such pathologies as addiction to nicotine other drugs of abuse. α-Conotoxin LvIA, which we previously isolated from Conus lividus, modestly discriminates rat nAChRs exhibiting a ∼17-fold tighter binding former. Here, alanine scanning resulted two more selective analogues [N9A]LvIA [D11A]LvIA, former having...
α3β4 nAChRs have been implicated in various pathophysiological conditions. However, the expression profile of and α6/α3β4 overlap a variety tissues. To distinguish between these two subtypes, we redesigned peptide 1 (α-conotoxin TxID), which inhibits nAChR subtypes. We systematically mutated to evaluate analogue selectivity for vs expressed Xenopus laevis oocytes. One analogue, 7 ([S9A]TxID), had 46-fold greater potency versus nAChRs. Peptide IC50s > 10 μM other Molecular dynamics...
Specific interaction between the postsynaptic density protein 95 (PSD95) and synapse-associated 90/postsynaptic 95-associated (SAPAP) is crucial for excitatory synaptic development plasticity. Designing inhibitors that target guanylate kinase (GK) domain of PSD95, which responsible interaction, a promising manipulation tool investigation function PSD95 GK etiology its related psychiatric disorders. Herein, we designed new peptide GK/SAPAP with higher binding affinity by using molecular...
The α3β4 nicotinic acetylcholine receptor (nAChR) is an important target implicated in various disease states. α-Conotoxin TxID (1) the most potent antagonist of nAChR, but it also exhibits inhibition α6/α3β4 nAChR. results alanine scanning 1 suggested a vital role for Ser9 selectivity peptide. In this study, was substituted with series 14 amino acids, including some non-natural displaying different physicochemical characteristics to further improve toward pharmacological activities mutants...
αO-conotoxin GeXIVA from Conus generalis is a potent antagonist of the α9α10 nAChR and analgesic in animal models pain. This peptide has two disulfide bond cross-links, bead ribbon isomers have similar inhibitory activity against nAChRs. We synthesized 12 disulfide-deficient analogues GeXIVA, all remained inhibitors nAChR. The most analogue displayed IC50 values 6 33 nM at rat human nAChRs, respectively, representing less than 2-fold increase compared with GeXIVA. analogs parent peptides...
The O‐superfamily of conotoxins includes several subfamilies with different pharmacological targets, all which are voltage‐gated ion channels and distributed widely in varied Conus species. venom components from any species quite distinct those other Seven novel peptides were identified by cDNA cloning the three vermivorous C. betulinus , lividus caracteristicus native to Hainan. They share common signal sequences, a conserved arrangement cysteine residues (C–C–CC–C–C). Phylogenetic analysis...
α6β4 nicotinic acetylcholine receptors (nAChRs) are expressed in the central and peripheral nervous systems, but their functions not fully understood, largely because of a lack specific ligands. Here, we characterized novel α-conotoxin, LvIC, designed series analogues to probe structure–activity relationships at nAChR. The potency selectivity these conotoxins were tested using two-electrode voltage-clamp recording on nAChR subtypes Xenopus laevis oocytes. One analogues, [D1G,ΔQ14]LvIC,...
αO-Conotoxin GeXIVA is a selective α9α10 nicotinic acetylcholine receptor (nAChR) inhibitor displaying two disulfide bonds that can form three isomers. The bead (GeXIVA[1,2]) and ribbon (GeXIVA[1,4]) isomers possess the highest activity on rat human nAChRs. However, molecular mechanism by which they inhibit nAChR unknown. Here, an alanine scan of was used to elucidate key interactions between peptides nAChR. majority GeXIVA[1,2] analogues preserved affinity at nAChR, but [R17A]GeXIVA[1,2]...
The α7 nicotinic acetylcholine receptor (nAChR) is present in the central nervous system and plays an important role cognitive function memory. α-Conotoxin LvIB, identified from genomic DNA of Conus lividus, its three isomers four globular isomer analogues were synthesized screened at a wide range nAChR subtypes. One analogues, amidated [Q1G,ΔR14]LvIB, was found to be potent blocker rat nAChRs. Importantly, it differentiates between nAChRs human (IC50: 1570 nM) 97 nM). Substitutions key...
α6β4* nicotinic acetylcholine receptor (nAChR) (* represents the possible presence of additional subunits) is mainly distributed in central and peripheral nervous system associated with neurological diseases, such as neuropathic pain; however, ability to explore its function distribution limited due lack pharmacological tools. As one analogs α-conotoxin (α-CTx) LvIC from Conus lividus, [D1G, Δ14Q]LvIC (Lv) selectively potently blocks α6/α3β4 nAChR (α6/α3 a chimera). Here, we synthesized...
Nicotinic acetylcholine receptors (nAChRs) are essential pentameric ligand-gated ion channels that distributed throughout the central and peripheral nervous systems non-neuronal tissues in mammalian species play critical roles a variety of neural mental activities. The α3β2 nAChR subtype participates pain, addiction to nicotine, other neurophysiological pathological Owing lack highly selective pharmacological tools targeting α3β2, related research on its tissue distribution function has been...
Oligo-basic amino acids have been extensively studied in molecular biology and pharmacology, but the inhibitory activity on nicotinic acetylcholine receptors (nAChRs) was unknown. In this study, of 8 oligopeptides, including both basic acidic acids, evaluated 9 nAChR subtypes by a two-electrode voltage clamp (TEVC). Among them, oligo-lysine K9, K12, d-K9, d-K9F, oligo-arginine R9 showed nanomolar various nAChRs, especially for α7 α9α10 nAChRs. d-K9 containing N-Fmoc protecting group (d-K9F)...
The coexistence of two or more distinct neoplasms within the same anatomical site characterizes collision tumors. While presence dual tumors is frequently observed in esophageal cases, simultaneous occurrence three tumor types extremely rare, posing significant challenges for pathological evaluation and diagnosis. Surgical resection remains primary treatment, with generally favorable outcomes.