Surface Plasmon Resonance Approach Research Articles

Enhancing Precision in Fuel Adulteration Detection: Utilizing a Wavelength Interrogation Surface Plasmon Resonance Approach

Enhancing Precision in Fuel Adulteration Detection: Utilizing a Wavelength Interrogation Surface Plasmon Resonance Approach

Electrochemical surface plasmon resonance approach to probe redox interactions between microbial extracellular polymeric substances and p-nitrophenol

Microbial extracellular polymeric substances with redox functional groups play a crucial role in the bio-conversion of pollutants, which can affect their reactivity toward diverse pollutants. However, the redox interactions between microbial EPS and pollutants have not addressed in depth due to the absence of essential analytical methodologies. In this study, we have developed an electrochemical-surface plasmon resonance (EC-SPR) system to investigate the interactions between EPS and p-nitrophenol (PNP) by simultaneously monitoring the electrochemical reaction and the binding kinetics. Moreover, in vitro PNP degradation experiments were performed in the presence of EPS across varying redox states to provide further verification of PNP reduction by EPS. The results indicated that direct electrochemical treatment successfully converted raw EPS (EPSraw) into reductive EPS (EPSred) and oxidized EPS (EPSox), respectively. The EC-SPR system served as a powerful tool for probing redox interactions between EPS at distinct redox states and PNP. The binding affinity of EPS to PNP was related to the redox states of EPS, following the order of EPSred > EPSraw > EPSox. EPS exhibited the capability to reduce PNP to p-aminophenol by donating electrons, and the reductive process highly depended on the redox states of EPS, primarily determined by their electron donating capacity. Importantly, direct electrochemical reduction treatment of EPS leads to a substantial improvement in the PNP removal efficiency from 33.8% (EPSraw) to 56.9% (EPSred). This work contributes to a comprehensive understanding of the critical role of EPS redox property in the conversion of refractory pollutants in aquatic environments.

Detection of Various Traditional Chinese Medicinal Metabolites as Angiotensin-Converting Enzyme Inhibitors: Molecular Docking, Activity Testing, and Surface Plasmon Resonance Approaches.

Angiotensin-converting enzyme 1 (ACE1) is a peptide involved in fluid and blood pressure management. It regulates blood pressure by converting angiotensin I to angiotensin II, which has vasoconstrictive effects. Previous studies have shown that certain compounds of natural origin can inhibit the activity of angiotensin-converting enzymes and exert blood pressure-regulating effects. Surface Plasmon Resonance (SPR) biosensor technology is the industry standard method for observing biomolecule interactions. In our study, we used molecular simulation methods to investigate the docking energies of various herbal metabolites with ACE1 proteins, tested the real-time binding affinities between various herbal metabolites and sACE1 by SPR, and analyzed the relationship between real-time binding affinity and docking energy. In addition, to further explore the connection between inhibitor activity and real-time binding affinity, several herbal metabolites' in vitro inhibitory activities were tested using an ACE1 activity test kit. The molecular docking simulation technique's results and the real-time affinity tested by the SPR technique were found to be negatively correlated, and the virtual docking technique still has some drawbacks as a tool for forecasting proteins' affinities to the metabolites of Chinese herbal metabolites. There may be a positive correlation between the enzyme inhibitory activity and the real-time affinity detected by the SPR technique, and the results from the SPR technique may provide convincing evidence to prove the interaction between herbal metabolites and ACE1 target proteins.

Surface plasmon resonance and microscale thermophoresis approaches for determining the affinity of perforin for calcium ions.

Perforin is a pore-forming protein that plays a crucial role in the immune system by clearing virus-infected or tumor cells. It is released from cytotoxic granules of immune cells and forms pores in targeted lipid membranes to deliver apoptosis-inducing granzymes. It is a very cytotoxic protein and is therefore adapted not to act in producing cells. Its activity is regulated by the requirement for calcium ions for optimal activity. However, the exact affinity of perforin for calcium ions has not yet been determined. We conducted a molecular dynamics simulation in the absence or presence of calcium ions that showed that binding of at least three calcium ions is required for stable perforin binding to the lipid membrane. Biophysical studies using surface plasmon resonance and microscale thermophoresis were then performed to estimate the binding affinities of native human and recombinant mouse perforin for calcium ions. Both approaches showed that mouse perforin has a several fold higher affinity for calcium ions than that of human perforin. This was attributed to a particular residue, tryptophan at position 488 in mouse perforin, which is replaced by arginine in human perforin. This represents an additional mechanism to control the activity of human perforin.

Surface plasmon resonance based-optical biosensor: Emerging diagnostic tool for early detection of diseases.

The development of diagnostic tools remains at the center of the health care system. In recent times optical biosensors have been widely applied in the scientific community, especially for monitoring protein-protein or nucleic acid hybridization interactions. Optical biosensors-derived surface plasmon resonance (SPR) technology has appeared as a revolutionary technology at the current times. This review focuses on the research work in molecular biomarker evaluation using the technique based on SPR for translational clinical diagnosis. The review has covered both communicable and noncommunicable diseases by using different bio-fluids of the patient's sample for diagnosis of the diseases. An increasing number of SPR approaches have been developed in healthcare research and fundamental biological studies. The utility of SPR in the area of biosensing basically lies in its noninvasive diagnostic and prognostic feature due to its label-free high sensitivity and specificity properties. This makes SPR an invaluable tool with precise application in the recognition of different stages of the disease.

The RNA-Binding and RNA-Melting Activities of the Multifunctional Protein Nucleobindin 1

Nucleobindin 1 (NUCB1) is a ubiquitous multidomain protein that belongs to the EF-hand Ca2+-binding superfamily. NUCB1 interacts with Galphai3 protein, cyclooxygenase, amyloid precursor protein, and lipids. It is involved in stress response and human diseases. In addition, this protein is a transcription factor that binds to the DNA E-box motif. Using surface plasmon resonance and molecular beacon approaches, we first showed the RNA binding and RNA melting activities of NUCB1. We suggest that NUCB1 could induce local changes in structured RNAs via binding to the GGAUAU loop sequence. Our results demonstrate the importance of the multidomain structure of NUCB1 for its RNA-chaperone activity in vitro.

Exploring novel targets of sitagliptin for type 2 diabetes mellitus: Network pharmacology, molecular docking, molecular dynamics simulation, and SPR approaches.

Diabetes has become a serious global public health problem. With the increasing prevalence of type 2 diabetes mellitus (T2DM), the incidence of complications of T2DM is also on the rise. Sitagliptin, as a targeted drug of DPP4, has good therapeutic effect for T2DM. It is well known that sitagliptin can specifically inhibit the activity of DPP4 to promote insulin secretion, inhibit islet β cell apoptosis and reduce blood glucose levels, while other pharmacological mechanisms are still unclear, such as improving insulin resistance, anti-inflammatory, anti-oxidative stress, and anti-fibrosis. The aim of this study was to explore novel targets and potential signaling pathways of sitagliptin for T2DM. Firstly, network pharmacology was applied to find the novel target most closely related to DPP4. Semi-flexible molecular docking was performed to confirm the binding ability between sitagliptin and the novel target, and molecular dynamics simulation (MD) was carried to verify the stability of the complex formed by sitagliptin and the novel target. Furthermore, surface-plasmon resonance (SPR) was used to explored the affinity and kinetic characteristics of sitagliptin with the novel target. Finally, the molecular mechanism of sitagliptin for T2DM was predicted by the enrichment analysis of GO function and KEGG pathway. In this study, we found the cell surface receptor-angiotensin-converting enzyme 2 (ACE2) most closely related to DPP4. Then, we confirmed that sitagliptin had strong binding ability with ACE2 from a static perspective, and the stability of sitagliptin-ACE2 complex had better stability and longer binding time than BAR708-ACE2 in simulated aqueous solution within 50 ns. Significantly, we have demonstrated a strong affinity between sitagliptin and ACE2 on SPR biosensor, and their kinetic characteristics were "fast binding/fast dissociation". The guiding significance of clinical administration: low dose can reach saturation, but repeated administration was needed. Finally, there was certain relationship between COVID-19 and T2DM, and ACE2/Ang-(1-7)/Mas receptor (MasR) axis may be the important pathway of sitagliptin targeting ACE2 for T2DM. This study used different methods to prove that ACE2 may be another novel target of sitagliptin for T2DM, which extended the application of ACE2 in improving diabetes mellitus.

Adsorption independent silver colloids index measurement with metal-cladding optical waveguide

The refractive index measurements of silver nanoparticles colloids can provide chemical composition and nanostructure details. Although the standard surface plasmon resonance (SPR) approach improves index measurement precision, it is restricted by silver nanoparticles adsorption and incapable of detecting the colloid index due to the evanescent nature of the surface wave. Herein, a method utilizing metal-cladding optical waveguide (MCOW) was proposed to measure the volume refractive index of silver nanoparticles colloids, importantly, which is independent of particle adsorption. The experimental results show that the sensitivity of the refractive index measurement using the MCOW approach is at least 10−6 RIU (Refractive Index Unit) owing to the oscillating ultrahigh-order modes, this work not only presents a high-sensitivity, high-yield, simple-to-process, and effective refractive index measuring technique, but also recommends a more practical and adaptable colloidal particle characterization approach.

Interaction of Escherichia coli heat-labile enterotoxin B-pentamer with exopolysaccharides from Leuconostoc mesenteroides P35: Insights from surface plasmon resonance and molecular docking studies

In this study, the interaction of exopolysaccharides from Leuconostoc mesenteroides P35 (EPS-LM) with Escherichia coli heat-labile enterotoxin B-pentamer (LTB) was investigated at different concentrations and temperatures by using surface plasmon resonance (SPR) and molecular docking approaches. FT-IR spectral analysis together with HPTLC analysis revealing that glucose is the only constitutive monosaccharide of EPS-LM suggests that its structure is composed of dextran with α-D (1 → 6) glycosidic linkages. SPR analysis revealed the high affinity of EPS-LM for immobilized LTB toxin (KA=(2.05 ± 0.04) × 106 mol.L−1 at 37°C). The binding process was spontaneous (ΔG<0), endothermic (ΔH>0), and entropy-driven (ΔS>0) with an increase of KA with temperature. This suggests that EPS-LM - LTB interaction is dominated by hydrophobic forces. The binding affinity of EPS-LM to LTB had negligible dependence on enthalpy (ΔH = 0.084 kJ mol−1). Further, molecular docking results suggested the presence of some binding sites of EPS-LM on the LTB through hydrophobic forces (Lys, Asp, Arg, Glu) and also hydrogen bonding (Glu) in the hydrophobic core of LTB. Besides autodock studies, Schiffer-Edmundson helical wheel diagrams of LTB in α-helix domain suggested that LTB hydrophobic core is a highly effective region, which was able to form favorable non-polar interactions of the protein's binding surface (with amino acids residues such as Tyr, Leu, Ile) with EPS-LM. This study provided thus further insights into the interactions between EPS-LM and LTB, suggesting that EPS produced by some LAB, such as EPS produced by Ln. mesenteroides P35 strain are good candidates to inhibit E. coli toxin activity.

Mechanisms of Influenza Virus HA2 Peptide Interaction with Liposomes Studied by Dual-Wavelength MP-SPR.

A phospholipid-based liposome layer was used as an effective biomimetic membrane model to study the binding of the pH-dependent fusogenic peptide (E4-GGYC) from the influenza virus hemagglutinin HA2 subunit. To this end, a multiparameter surface plasmon resonance approach (MP-SPR) was used for monitoring peptide-liposome interactions at two pH values (4.5 and 8) by means of recording sensorgrams in real time without the need for labeling. Biotinylated liposomes were first immobilized as a monolayer onto the surface of an SPR gold chip coated with a streptavidin layer. Multiple sets of sensorgrams with different HA2 peptide concentrations were generated at both pHs. Dual-wavelength Fresnel layer modeling was applied to calculate the thickness (d) and the refractive index (n) of the liposome layer to monitor the change in its optical parameters upon interaction with the peptide. At acidic pH, the peptide, in its α helix form, entered the lipid bilayer of liposomes, inducing vesicle swelling and increasing membrane robustness. Conversely, a contraction of liposomes was observed at pH 8, associated with noninsertion of the peptide in the double layer of phospholipids. The equilibrium dissociation constant KD = 4.7 × 10-7 M of the peptide/liposome interaction at pH 4.5 was determined by fitting the "OneToOne" model to the experimental sensorgrams using Trace Drawer software. Our experimental approach showed that the HA2 peptide at a concentration up to 100 μM produced no disruption of liposomes at pH 4.5.

A computational approach to rapidly design peptides that detect SARS-CoV-2 surface protein S

The coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prompted the development of diagnostic and therapeutic frameworks for timely containment of this pandemic. Here, we utilized our non-conventional computational algorithm, InSiPS, to rapidly design and experimentally validate peptides that bind to SARS-CoV-2 spike (S) surface protein. We previously showed that this method can be used to develop peptides against yeast proteins, however, the applicability of this method to design peptides against other proteins has not been investigated. In the current study, we demonstrate that two sets of peptides developed using InSiPS method can detect purified SARS-CoV-2 S protein via ELISA and Surface Plasmon Resonance (SPR) approaches, suggesting the utility of our strategy in real time COVID-19 diagnostics. Mass spectrometry-based salivary peptidomics shortlist top SARS-CoV-2 peptides detected in COVID-19 patients’ saliva, rendering them attractive SARS-CoV-2 diagnostic targets that, when subjected to our computational platform, can streamline the development of potent peptide diagnostics of SARS-CoV-2 variants of concern. Our approach can be rapidly implicated in diagnosing other communicable diseases of immediate threat.

Discovery and biological evaluation of tanshinone derivatives as potent dual inhibitors of indoleamine 2, 3-dioxygenase 1 and tryptophan 2, 3-dioxygenase

Indoleamine 2, 3-dioxygenase 1 (IDO1) and tryptophan 2, 3-dioxygenase (TDO), catalyzing the first and rate-limiting step of tryptophan-kynurenine (Trp-Kyn) metabolism pathway, are the appealing targets for cancer immunotherapy. A few dual IDO1/TDO inhibitors are reported in literature. However, small-molecule IDO1 and TDO inhibitors are not yet available for clinical use. Here, we report synthetic analogues of the naturally occurring terpenoids tanshinone IIA and crytotanshinone, and their IDO1/TDO inhibitory activities using enzymatic and cellular assays. The most potent compound 30 was further characterized with respect to the direct interaction, inhibition kinetics, and different binding modes against IDO1 and TDO through surface plasmon resonance (SPR), enzyme kinetics, and spectroscopic analysis approaches, respectively. Preliminary mechanistic studies showed that 30 significantly promoted cell apoptosis through the potential mitochondria-mediated Bcl-2/Bax pathway. IDO1-overexpressing HeLa cells, mimicking cancer cells, were sensitive to 30 treatments. These results provide further insights for new clinical application of tanshinones, the main component of traditional herbal medicine.

Mechanism of Paeoniae Radix Alba in the Treatment of Non-alcoholic Fatty Liver Disease Based on Sequential Metabolites Identification Approach, Network Pharmacology, and Binding Affinity Measurement.

Screening functional food ingredients (FFI) from medicinal and edible plants (MEP) has still remained a great challenge due to the complexity of MEP and its obscure function mechanisms. Herein, an integrated strategy based on sequential metabolites identification approach, network pharmacology, molecular docking, and surface plasmon resonance (SPR) analysis was proposed for quickly identifying the active constituents in MEP. First, the sequential biotransformation process of MEP, including intestinal absorption and metabolism, and hepatic metabolism, was investigated by oral gavage, and intestinal perfusion with venous sampling method. Then the blood samples were analyzed by UPLC-Q Exactive Orbitrap HRMS. Second, the network pharmacology approach was used to explore the potential targets and possible mechanisms of the in vivo metabolites of MEP. Third, molecular docking and SPR approaches were used to verify the specific interactions between protein targets and representative ingredients. The proposed integrated strategy was successfully used to explore the heptoprotective components and the underlying molecular mechanism of Paeoniae Radix Alba (PRA). A total of 44 compounds were identified in blood samples, including 17 porotypes and 27 metabolites. The associated metabolic pathways were oxidation, methylation, sulfation, and glucuronidation. After further screening, 31 bioactive candidates and 377 related targets were obtained. In addition, the bioactive components contained in PRA may have therapeutic potentials for non-alcoholic fatty liver disease (NAFLD). The above results demonstrated the proposed strategy may provide a feasible tool for screening FFI and elaborating the complex function mechanisms of MEP.

Surface plasmon resonance approach to study drug interactions with SARS-CoV-2 RNA-dependent RNA polymerase highlights treatment potential of suramin

The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is essential for virus replication, therefore it is a promising drug target. Here we present a surface plasmon resonance approach to study the interaction of RdRp with drugs in real time. We monitored the effect of favipiravir, ribavirin, sofosbuvir triphosphate PSI-7409 and suramin on RdRp binding to RNA immobilized on the chip. Suramin precluded interaction of RdRp with RNA and even displaced RdRp from RNA.

Thermodynamic and kinetic insights into the interactions between functionalized CdTe quantum dots and human serum albumin: A surface plasmon resonance approach

To explore in vivo application of quantum dots (QDs), it is essential to understand the dynamics and energetics of interactions between QDs and proteins. Here, surface plasmon resonance (SPR) and molecular docking were employed to investigate the kinetics and thermodynamics of interactions between human serum albumin (HSA) and CdTe QDs (~3 nm) functionalized with mercaptopropionic acid (MPA) or thioglycolic acid (TGA). Kinetic analysis showed that HSA–QD interactions involved transition-complex formation. Despite the structural similarities between MPA and TGA, the [HSA−CdTe@TGA]‡ formation by association of free HSA and QDs demanded 70% more energy and higher entropic gain (Ea−TGA‡= 65.10 and T∆Sa−TGA‡= 28.62 kJ mol−1) than the formation of [HSA−CdTe@MPA]‡ (Ea−MPA‡ = 38.13 and T∆Sa−MPA‡ = 0.53kJ mol−1). While the [HSA−CdTe@MPA]° dissociation required higher energy and lower entropy loss (Ed−MPA‡ = 49.96 and T∆Sd−MPA‡ = − 32.18kJ mol−1) than the [HSA−CdTe@TGA]° dissociation (Ed−TGA‡= 30.78 and T∆Sd−TGA‡= − 51.12 kJ mol−1). The stability of [HSA−QDs]° was independent of the temperature and functionalizing group. However, the enthalpic and entropic components were highly affected by the substitution of MPA (ΔH° = − 11.83 and TΔS° = 32.72 kJ mol−1) with TGA (ΔH° = 34.31 and TΔS° = 79.73 kJ mol−1). Furthermore, molecular docking results indicated that the metal site on the QDs contributes to the stabilization of [HSA−QDs]°. Therefore, differences in QD functionalization and surface coverage densities can alter the HSA–QD interaction, thus their application.

Integrated Systems Pharmacology and Surface Plasmon Resonance Approaches to Reveal the Synergistic Effect of Multiple Components of Gu-Ben-Ke-Chuan Decoction on Chronic Bronchitis

IntroductionGu-Ben-Ke-Chuan (GBKC) decoction, a well-known prescription composed of seven herbs, has been widely used for treating chronic bronchitis (CB). However, the pharmacological constituents of GBKC and the underlying mechanisms by which these components act on CB remain unclear.MethodsUltra-high-pressure liquid chromatography coupled with linear ion trap–Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap) was first employed to rapidly identify compounds from GBKC. Thereafter, network pharmacology and molecular docking analyses were performed to identify the potential active constituents, candidate targets, and major pathways. Finally, the affinities between the key compounds and targets were verified via surface plasmon resonance (SPR) analysis. In addition, the anti-inflammatory effect of GBKC was verified using an LPS-induced inflammatory cell model based on the predicted results.ResultsA total of 53 major compounds were identified in the GBKC decoction. After network pharmacology-based virtual screening, 141 major targets and 39 main compounds were identified to be effective in the treatment of CB. The major targets were highly enriched in the tumor necrosis factor (TNF) signaling pathway, suggesting that GBKC could attenuate the inflammatory response in patients with CB. Furthermore, molecular docking results indicated that 20 pairs of components and target proteins relevant to the TNF pathway exhibited notable interactions. Among them, eight compound-target pairs exhibited good affinity as per SPR analysis. In addition, the production of interleukin 6 and TNF-α in LPS-induced MH-S cells was suppressed after GBKC treatment.ConclusionThis study successfully clarified the mechanism of action of GBKC against CB, which demonstrated that the integrated strategy described above is reliable for identifying the active compounds and mechanisms responsible for the pharmacological activities of GBKC decoction.

Limonoids from Guarea guidonia and Cedrela odorata: Heat Shock Protein 90 (Hsp90) Modulator Properties of Chisomicine D.

Nine new limonoids (1–9) were isolated from the stem bark of Guarea guidonia (1–4) and Cedrela odorata (5–9). Their structures were elucidated using 1D and 2D NMR and MS data and chemical methods as three A2,B,D-seco-type limonoids (1–3), a mexicanolide (4), three nomilin-type (5–7) limonoids, and two limonol derivatives (8 and 9). A DFT/NMR procedure was used to define the relative configurations of 1 and 3. A surface plasmon resonance approach was used to screen the Hsp90 binding capability of the limonoids, and the A2,B,D-seco-type limonoid 8-hydro-(8S*,9S*)-dihydroxy-14,15-en-chisomicine A, named chisomicine D (1), demonstrated the highest affinity. By means of mass spectrometry data, biochemical and cellular assays, and molecular docking, 1 was found as a type of client-selective Hsp90 inhibitor binding to the C-terminus domain of the chaperone.

Affinity-Based Nanoarchitectured Biotransducer for Sensitivity Enhancement of Surface Plasmon Resonance Sensors for In Vitro Diagnosis: A Review.

Despite the indisputable benefits and advancement of science, technology, and civilization, early diagnosis of healthcare is still a challenging field for the scientific fraternity. The detection of biomarkers is a crucial attribute of prognosis and diagnosis of disease. Out of numerous techniques, surface plasmon resonance (SPR) bestows countless benefits, including in situ, label-free, and real-time assessment, etc., which authorizes the analysis of molecular binding occurrences between biotransducers and biomarkers. In addition, SPR with low-molecular-weight biomarkers lacks selectivity and sensitivity, which ultimately affects binding kinetics. This, in turn, leads to the remarkable development and implementation of numerous selectivity and sensitivity enhancement methods. Among the various noticeable strategies, because of selectivity and sensitivity enrichment substrate for SPR biosensors, affinity-based nanoarchitectured biotransducers stand out as being the best substitute. The present review elaborates significant advances made in the research based on affinity biotransducers for in vitro diagnosis using SPR biosensors for biomarker sensing. Moreover, most recent trends and challenges in designing and application of nanoarchitectured affinity biotransducer-based SPR biosensors for detecting low-concentration biomarkers have been reviewed comprehensively. This present review may assist the scientific fraternity in designing an ultramodern novel SPR approach based on affinity biotransducers, along with improved selectivity and sensitivity of SPR biosensors for in vitro and real-time diagnostic applications.

Toll-like receptor 4-mediated inflammation triggered by extracellular IFI16 is enhanced by lipopolysaccharide binding.

Damage-associated molecular patterns (DAMPs) are endogenous molecules activating the immune system upon release from injured cells. Here we show that the IFI16 protein, once freely released in the extracellular milieu of chronically inflamed tissues, can function as a DAMP either alone or upon binding to lipopolysaccharide (LPS). Specifically, using pull-down and saturation binding experiments, we show that IFI16 binds with high affinity to the lipid A moiety of LPS. Remarkably, IFI16 DAMP activity is potentiated upon binding to subtoxic concentrations of strong TLR4-activating LPS variants, as judged by TLR4-MD2/TIRAP/MyD88-dependent IL-6, IL-8 and TNF-α transcriptional activation and release in stimulated monocytes and renal cells. Consistently, using co-immunoprecipitation (co-IP) and surface plasmon resonance (SPR) approaches, we show that IFI16 is a specific TLR4-ligand and that IFI16/LPS complexes display a faster stimulation turnover on TLR4 than LPS alone. Altogether, our findings point to a novel pathomechanism of inflammation involving the formation of multiple complexes between extracellular IFI16 and subtoxic doses of LPS variants, which then signal through TLR4.

Tetrapeptide Ac-HAEE-NH2 Protects α4β2 nAChR from Inhibition by Aβ.

The cholinergic deficit in Alzheimer’s disease (AD) may arise from selective loss of cholinergic neurons caused by the binding of Aβ peptide to nicotinic acetylcholine receptors (nAChRs). Thus, compounds preventing such an interaction are needed to address the cholinergic dysfunction. Recent findings suggest that the 11EVHH14 site in Aβ peptide mediates its interaction with α4β2 nAChR. This site contains several charged amino acid residues, hence we hypothesized that the formation of Aβ-α4β2 nAChR complex is based on the interaction of 11EVHH14 with its charge-complementary counterpart in α4β2 nAChR. Indeed, we discovered a 35HAEE38 site in α4β2 nAChR, which is charge-complementary to 11EVHH14, and molecular modeling showed that a stable Aβ42-α4β2 nAChR complex could be formed via the 11EVHH14:35HAEE38 interface. Using surface plasmon resonance and bioinformatics approaches, we further showed that a corresponding tetrapeptide Ac-HAEE-NH2 can bind to Aβ via 11EVHH14 site. Finally, using two-electrode voltage clamp in Xenopus laevis oocytes, we showed that Ac-HAEE-NH2 tetrapeptide completely abolishes the Aβ42-induced inhibition of α4β2 nAChR. Thus, we suggest that 35HAEE38 is a potential binding site for Aβ on α4β2 nAChR and Ac-HAEE-NH2 tetrapeptide corresponding to this site is a potential therapeutic for the treatment of α4β2 nAChR-dependent cholinergic dysfunction in AD.