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A novel promoter system for glycosylation is described. A catalytic amount of thiourea and Cu(OTf)2 together with a slight excess of N-iodosuccinimide synergistically promotes glycosylation at room temperature. The combination of reagents applies to some 2-azidoselenoglycoside and thioglycoside donors. A wide range of alcoholic acceptors underwent smooth conversion to O-(2-azido)glycosides with good stereoselectivities. In addition, the value of this method has been highlighted by its convenient operation and outstanding functional group compatibility.
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3,5-Di(trifluoromethyl)phenyl(cyano)iodonium triflate is described as an accessible, stable, and powerful thiophile that can activate batches of p-tolyl thioglycoside donors at room temperature. Various alcoholic acceptors were efficiently glycosylated, providing the desired glycosides. The novel activation protocol features mild conditions as well as high compatibility with some classic strategies for the stereoselective construction of some biologically relevant glycosidic linkages, as exemplified by α-idosides, α-galactoamines, ß-mannosides, and ß-rhamnosides.
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In medical and material science, 3D reconstruction is of great importance for quantitative analysis of microstructures. After the image segmentation process of serial slices, in order to reconstruct each local structure in volume data, it needs to use precise object tracking algorithm to recognize the same object region in adjacent slice. Suffering from weak representative hand-crafted features, traditional object tracking methods always draw out under-segmentation results. In this work, we have proposed an adjacent similarity based deep learning tracking method (ASDLTrack) to reconstruct 3D microstructure. By transferring object tracking problem to classification problem, it can utilize powerful representative ability of convolutional neural network in pattern recognition. Experiments in three datasets with three metrics demonstrate that our algorithm achieves the promising performance compared to traditional methods.
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Aprendizaje Profundo , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Redes Neurales de la ComputaciónRESUMEN
Identifying protein post-translational modifications (PTMs) from tandem mass spectrometry data of complex proteome mixtures is a highly challenging task. Here we present a new strategy, named iterative search for identifying PTMs (ISPTM), for tackling this challenge. The ISPTM approach consists of a basic search with no variable modification, followed by iterative searches of many PTMs using a small number of them (usually two) in each search. The performance of the ISPTM approach was evaluated on mixtures of 70 synthetic peptides with known modifications, on an 18-protein standard mixture with unknown modifications and on real, complex biological samples of mouse nuclear matrix proteins with unknown modifications. ISPTM revealed that many chemical PTMs were introduced by urea and iodoacetamide during sample preparation and many biological PTMs, including dimethylation of arginine and lysine, were significantly activated by Adriamycin treatment in nuclear matrix associated proteins. ISPTM increased the MS/MS spectral identification rate substantially, displayed significantly better sensitivity for systematic PTM identification compared with that of the conventional all-in-one search approach, and offered PTM identification results that were complementary to InsPecT and MODa, both of which are established PTM identification algorithms. In summary, ISPTM is a new and powerful tool for unbiased identification of many different PTMs with high confidence from complex proteome mixtures.
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Mapeo Peptídico/métodos , Procesamiento Proteico-Postraduccional , Proteoma/química , Programas Informáticos , Algoritmos , Secuencia de Aminoácidos , Animales , Línea Celular , Cromatografía por Intercambio Iónico , Ratones , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/aislamiento & purificación , Proteolisis , Proteoma/aislamiento & purificación , Proteoma/metabolismo , Curva ROC , Motor de Búsqueda , Espectrometría de Masas en Tándem , Tripsina/químicaRESUMEN
Pax5/B cell lineage specific activator protein (BSAP) is a B lineage-specific regulator that controls the B lineage-specific gene expression program and immunoglobulin gene V(H) to DJ(H) recombination. Despite extensive studies on its multiple functions, little is known about how the activity of Pax5 is regulated. Here, we show that co-expression of histone acetyltransferase E1A binding protein p300 dramatically enhances Pax5-mediated transcriptional activation. The p300-mediated enhancement is dependent on its intrinsic histone acetyltransferase activity. Moreover, p300 interacts with the C terminus of Pax5 and acetylates multiple lysine residues within the paired box DNA binding domain of Pax5. Mutations of lysine residues 67 and 87/89 to alanine within Pax5 abolish p300-mediated enhancement of Pax5-induced Luc-CD19 reporter expression in HEK293 cells and prevent Pax5 to activate endogenous Cd19 and Blnk expression in Pax5(-/-) murine pro B cells. These results uncover a novel level of regulation of Pax5 function by p300-mediated acetylation.
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Factor de Transcripción PAX5/metabolismo , Factores de Transcripción p300-CBP/metabolismo , Secuencia de Aminoácidos , Animales , Antígenos CD19/biosíntesis , Linfocitos B/citología , Humanos , Lisina/química , Ratones , Datos de Secuencia Molecular , Mutación , Unión Proteica , Estructura Terciaria de Proteína , Homología de Secuencia de AminoácidoRESUMEN
OBJECTIVE: To compare the clinical therapeutic effect and the impacts on recurrence rate on chronic spontaneous urticaria (CSU) between the combined treatment of bloodletting therapy and auricular point sticking on the base of xuanfu theory and the oral solution of levocetirizine hydrochloride. METHODS: A total of 86 patients with CSU were randomized into an observation group (43 cases, 1 case dropped off) and a control group (43 cases, 3 cases dropped off). In the observation group, bloodletting therapy at Dazhui (GV 14), Feishu (BL 13), Geshu (BL 17) and Pishu (BL 20) was combined with auricular point sticking at lung (CO14), kidney (CO10), shenmen (TF4) and heart (CO15), etc. This combined treatment was given once every two days. In the control group, the oral solution of levocetirizine hydrochloride was prescribed, 10 mL each time, once daily. The treatment lasted for 4 weeks in the two groups. Before and after treatment, urticaria activity score 7 (UAS7), the score of dermatology life quality index (DLQI) and the levels of serum immune globulin E (IgE), interleukin 4 (IL-4) and interferon γ (IFN-γ) were compared in the patients between the two groups. The clinical therapeutic effect was evaluated in patients of the two groups and the recurrence rate was followed up 4, 8 and 12 weeks after treatment separately. RESULTS: After treatment, the scores of UAS7 and DLQI, as well as the levels of serum IgE and IL-4 were all reduced as compared with those before treatment in the two groups (P<0.05), and the level of serum IFN-γ was increased (P<0.05). The total effective rate was 83.3% (35/42) in the observation group and was 85.0% (34/40) in the control group. There was no statistical significance for the difference in the clinical therapeutic effect between the two groups (P>0.05). Eight and 12 weeks after treatment, the recurrence rates were 21.1% (4/19) and 26.3% (5/19) in the observation group, lower than 55.0% (11/20) and 65.0% (13/20) in the control group, respectively (P<0.05). CONCLUSION: The combined therapy of bloodletting and auricular point sticking on the base of xuanfu theory relieves the clinical symptoms, regulates the levels of serum IgE, IL-4 and IFN-γ and improves the quality of life in the patients with CSU. The clinical therapeutic effect of this combined treatment is similar to the oral solution of levocetirizine hydrochloride. But, the recurrence rate of the combined treatment of bloodletting and auricular point sticking is lower and its long-term curative effect is better.
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Terapia por Acupuntura , Acupuntura Auricular , Urticaria Crónica , Puntos de Acupuntura , Venodisección , Humanos , Calidad de Vida , Resultado del TratamientoRESUMEN
A polymer-drug conjugate was developed by conjugating doxorubicin (DOX) to [alpha],[beta]-poly[(2-hydroxyethyl)-L-aspartamide] (PHEA) with a succinic spacer. The suitability of PHEA-DOX in intraperitoneal chemotherapy was investigated both in vitro and in vivo. The results showed that the release rate of DOX from PHEA-DOX in S180 ascites was faster than that in mouse serum or in buffer solutions. An in-vivo antitumor study revealed that PHEA-DOX was more effective than DOX against solid S180 tumor after intraperitoneal injection at the same dose of 10 or 15 mg (DOX eq.)/kg, respectively. At a high dose of 28 mg (DOX eq.)/kg, which was lethal for free DOX to mice, PHEA-DOX could inhibit 61.5% of solid S180 tumor growth and markedly prolonged the survival time of ascetic S180-bearing mice. The toxicological effects of PHEA-DOX injected intraperitoneally in normal mice were assessed by using LD50, body weight increment, electrocardiography, blood biochemical indices, and myocardium histology, giving evidence that PHEA-DOX displayed considerably reduced systemic and cardiotoxicity compared with free DOX. All results suggest that PHEA-DOX has great potential for intraperitoneal chemotherapy because of its high therapeutic effects and few adverse side effects.
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Antibióticos Antineoplásicos/uso terapéutico , Doxorrubicina/análogos & derivados , Péptidos/uso terapéutico , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/toxicidad , Línea Celular Tumoral , Citotoxinas/administración & dosificación , Citotoxinas/uso terapéutico , Citotoxinas/toxicidad , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Doxorrubicina/toxicidad , Femenino , Humanos , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos ICR , Péptidos/administración & dosificación , Péptidos/química , Péptidos/toxicidad , Sarcoma 180/tratamiento farmacológicoRESUMEN
OBJECTIVE: To compare the infuences on circadian rhythm of blood pressure in the patients with non-dipper essential hypertension between the combined treatment of time acupuncture and western medication and the simple western medication. METHODS: A total of 70 patients with non-dipper essential hypertension were randomized into an acupuncture plus western medication group (35 cases, 2 cases dropped out) and a western medication group (35 cases). In the western medication group, levamlodipine maleate tablets were taken orally, 2.5 mg each time, once daily. In the acupuncture plus western medication group, on the base of the treatment as the western medication group, acupuncture was applied specially in the period of the day from 7:00 am to 9:00 am. The acupoints included Fengchi (GB 20), Zhongwan (CV 12), Tianshu (ST 25), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), etc. Acupuncture was given once daily, 5 treatments a week. The duration of treatment in the two groups was 4 weeks. The clinic blood pressure before and after treatment, 24 h ambulatory blood pressure and the levels of serum melatonin (MT) and 5-serotonin (5-HT) were observed in the two groups. RESULTS: The total effective rate of anti-hypertension was 75.8% (25/33) in the acupuncture plus western medication group, better than 54.3% (19/35) in the western medication group (P<0.05). The 24 h average systolic blood pressure, the daytime average systolic blood pressure, the daytime average diastolic pressure, and the nighttime average systolic blood pressure were all reduced after treatment in the two groups (P<0.05). The reduction effect of the aforementioned 4 indexes in the acupuncture plus western medication group was much more obvious as compared with the western medication group (P<0.05). After treatment, the serum level of MT was increased and 5-HT decreased in the patients of two groups (P<0.05). The serum level of MT in the acupuncture plus western medication group was higher than that in the western medication group and the level of 5-HT was lower than the western medication group (P<0.05). CONCLUSION: Time acupuncture therapy in the period of the day from 7:00 am to 9:00 am, combined with western medication effectively reduce blood pressure and regulate the levels of serum MT and 5-HT so as to maintain the circadian rhythm of blood pressure in patients with non-dipper essential hypertension. The therapeutic effect of this combined treatment is superior to simple western medication.
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Terapia por Acupuntura , Hipertensión Esencial/terapia , Periodicidad , Puntos de Acupuntura , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Ritmo Circadiano , HumanosRESUMEN
Organophosphate (OP) esters bind covalently to the active site serine of enzymes in the serine hydrolase family. Recently, mass spectrometry identified covalent binding of OPs to tyrosine in a wide variety of proteins when purified proteins were incubated with OPs. In the current work, manual inspection of tandem mass spectrometry (MS/MS) data led to the realization that lysines also make a covalent bond with OPs. OP-labeled lysine residues were found in seven proteins that had been treated with either chlorpyrifos oxon (CPO) or diisopropylfluorophosphate (DFP): human serum albumin (K212, K414, K199, and K351), human keratin 1 (K211 and K355), human keratin 10 (K163), bovine tubulin alpha (K60, K336, K163, K394, and K401), bovine tubulin beta (K58), bovine actin (K113, K291, K326, K315, and K328), and mouse transferrin (K296 and K626). These results suggest that OP binding to lysine is a general phenomenon. Characteristic fragments specific for CPO-labeled lysine appeared at 237.1, 220.0, 192.0, 163.9, 128.9, and 83.9amu. Characteristic fragments specific for DFP-labeled lysine appeared at 164.0, 181.2, and 83.8amu. This new OP-binding motif to lysine suggests new directions to search for mechanisms of long-term effects of OP exposure and in the search for biomarkers of OP exposure.
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Lisina/metabolismo , Organofosfatos/metabolismo , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Secuencia de Aminoácidos , Animales , Bovinos , Cloropirifos/análogos & derivados , Cloropirifos/metabolismo , Humanos , Isoflurofato/metabolismo , Ratones , Datos de Secuencia Molecular , Proteínas/química , Coloración y Etiquetado , Espectrometría de Masas en TándemRESUMEN
Under the catalysis of DMAP or PPY in CH(2)Cl(2), the Michael-type addition of nucleophiles to 2-nitrogalactal or 2-nitroglucal leads in excellent yields and stereoselectivity to the corresponding beta-galacto- or -glucopyranosides, which are ready precursors to the biologically significant beta-d-galactosamine and -glucosamine units.
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Glucósidos/química , Piranos/química , Catálisis , Técnicas Químicas Combinatorias , Glucósidos/síntesis química , Glicosilación , Estructura Molecular , EstereoisomerismoRESUMEN
Topological grain forms in three dimensions are studied experimentally and by large-scale Potts model Monte Carlo simulation. Some new band-faced grain forms are firstly observed among 16,254 pure iron grains, yet none of them is found among 28,049 Monte Carlo simulation grains, which indicate that there is shorter residence times for band-faced grain forms in three dimensions. The combined curvature/topology analysis suggests a possible efficient way of topological transitions of grain forms which is different from the known transition paths.
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The inner structure of a material is called its microstructure. It stores the genesis of a material and determines all the physical and chemical properties. However, the microstructure is highly complex and numerous image defects such as vague or missing boundaries formed during sample preparation, which makes it difficult to extract the grain boundaries precisely. In this work, we address the task of grain boundary detection in microscopic image processing and develop a graph-cut based method called Fast-FineCut to solve the problem. Our algorithm makes two key contributions: (1) An improved approach that incorporates 3D information between slices as domain knowledge, which can detect the boundaries precisely, even for the vague and missing boundaries. (2) A local processing method based on overlap-tile strategy, which can not only solve the "chain scission" problem at the edge of images, but also economize on the consumption of computing resources. We conduct experiments on a stack of 296 slices of microscopic images of polycrystalline iron (1600â¯×â¯2800) and compare the performance against several state-of-the-art boundary detection methods. We conclude that Fast-FineCut can detect boundaries effectively and efficiently.
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Tyrosine 411 of human albumin is an established site for covalent attachment of 10-fluoroethoxyphosphinyl- N-biotinamidopentyldecanamide (FP-biotin), diisopropylfluorophosphate, chlorpyrifos oxon, soman, sarin, and dichlorvos. This work investigated the hypothesis that other residues in albumin could be modified by organophosphorus agents (OP). Human plasma was aggressively treated with FP-biotin; plasma proteins were separated into high and low abundant portions using a proteome partitioning antibody kit, and the proteins were digested with trypsin. The FP-biotinylated tryptic peptides were isolated by binding to monomeric avidin beads. The major sites of covalent attachment identified by mass spectrometry were Y138, Y148, Y401, Y411, Y452, S232, and S287 of human albumin. Prolonged treatment of pure human albumin with chlorpyrifos oxon labeled Y138, Y150, Y161, Y401, Y411, and Y452. To identify the most reactive residue, albumin was treated for 2 h with DFP, FP-biotin, chlorpyrifos oxon, or soman, digested with trypsin or pepsin, and analyzed by mass spectrometry. The most reactive residue was always Tyr 411. Diethoxyphosphate-labeled Tyr 411 was stable for months at pH 7.4. These results will be useful in the development of specific antibodies to detect OP exposure and to engineer albumin for use as an OP scavenger.
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Albúminas/química , Biotina/análogos & derivados , Compuestos Organofosforados/química , Serina/química , Tirosina/química , Biotina/química , Cloropirifos/análogos & derivados , Cloropirifos/química , Cromatografía Liquida , Cristalografía por Rayos X , Diclorvos/química , Humanos , Concentración de Iones de Hidrógeno , Isoflurofato/química , Modelos Moleculares , Estructura Molecular , Reproducibilidad de los Resultados , Sarín/química , Soman/química , Coloración y Etiquetado , Espectrometría de Masas en TándemRESUMEN
PSI, as the potential peptide-like intermediate, is subject to simple chemical modification in order to obtain good non-viral carriers for gene delivery. This paper describes the facile synthesis and preliminary evaluation of alpha,beta-poly (3-dimethylaminopropyl-D,L-aspartamide) (PDAI) as a vector. Reaction of PSI with 3-dimethylamino-1-propylamine afforded PDAI in N,N-dimethylformamide (DMF) solution. Such biophysical properties of PDAI/DNA complexes as the particle size and the zeta potential were determined by dynamic light scattering assay. The complexes prepared at weight ratios ranging from 2 to 3 have an average size of around 200 nm and a zeta potential of around 10.0 mV. Gel electrophoresis assays confirmed that PDAI could compact DNA to form the complexes and protect DNA from enzymatic degradation by DNase I at the weight ratio above 2.0. Furthermore, PDAI was found to transfect HepG2 cells at a much higher efficiency than commercially available polyethylenimine (PEI) (W(w)=75,000 Da). MTT cytotoxicity assay demonstrated that PDAI also showed much less toxicity than did PEI, suggesting that PDAI is a new class of transfection reagent to be used as a safe vector.
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Vectores Genéticos , Péptidos/administración & dosificación , Transfección/métodos , Supervivencia Celular/efectos de los fármacos , ADN/administración & dosificación , Humanos , Péptidos/toxicidadRESUMEN
A new, efficient method based on a series of matrices is introduced to completely describe the detailed topology of individual domains and their topology evolution in three-dimensional cellular structures. With this approach, we found a lot of new topological grain forms which are never reported before, i.e., there are total 8 and 32 topological forms for 7- and 8-faced grains respectively, other than the reported 7 and 27. This method is proved to be a practical tool to predict all possible grain forms efficiently. Moreover, a connectivity index of grain forms serves as a new convenient differentiator of different multicellular structures.
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Imagenología Tridimensional/métodos , Algoritmos , Bandas de MatrizRESUMEN
As one of the important founders of GAO's acupuncture academic school in YanZhao area, Professor GAO Yuchun 's experience of acupuncture for headache is summarized in this paper. In the opinion of Professor GAO, the treatment of headache should focus on eliminating evil and relieving pain, and the syndrome differentiation should be based on meridian differentiation, especially on three yang meridians of foot as well as liver meridian and kidney meridian. In the acupoint prescription, attention should be placed on strengthening the spleen and stomach. The midnight-midday ebb flow acupuncture is advocated. The combination between acupuncture order and movement of qi is emphasized. In the manipulation, the role of pressing hand, the stimulation during reinforcing and reducing methods, and needle-retention time are important. The breathing reinforcing and reducing method of acupuncture are also advocated.
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Terapia por Acupuntura , Cefalea/terapia , Puntos de Acupuntura , Terapia por Acupuntura/métodos , Femenino , Humanos , Meridianos , Persona de Mediana EdadRESUMEN
To introduce professor Gao Yuchun's clinical experience and treating characteristics of facial paralysis treated with acupuncture and moxibustion. Professor Gao pays attention to yangming when he selects acupoints for clinical syndrome, and directs acupoints selection based on syndrome differentiation in different levels of jingjin, meridians and zangfu; he praises opposing needling technique and reinforcing the deficiency and reducing the excess highly; the acupuncture manipulation is gentle,shallow and slow for reducing the healthy side and reinforcing the affected side, and through losing its excess to complement its deficiency; besides, he stresses needle retaining time and distinguishes reinforcing and reducing. Facial paralysis is treated with key factors such as acupoints selecting based on yangming, acupuncture manipulation, needle retaining time, etc. And the spleen and stomach is fine and good at transportation and transformation; the meridians is harmonious; the qi and blood is smooth. The clinical efficacy is enhanced finally.
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Terapia por Acupuntura/historia , Parálisis Facial/terapia , Puntos de Acupuntura , Terapia por Acupuntura/métodos , Anciano de 80 o más Años , China , Parálisis Facial/historia , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
Fe3O4 nanoparticles were modified with Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and Polyethylene glycol 400 (PEG400) by a facile one-pot homogeneous precipitation method, and were used as a novel nano-adsorbent for the removal of congo red (CR) from aqueous solutions. The polymer-modified composites were characterized by FTIR, TEM, TGA, XRD and VSM, and showed excellent adsorption efficiency for CR. The value of the maximum adsorption capacity calculated according to the Langmuir isotherm model were 1.895g/g, which are much high and about 19 times that of Fe3O4 nanoparticles. Desorption study further indicates the good regeneration ability of the nanocomposites. The results suggest that the HP-ß-CD/PEG400-modified Fe3O4 nanoparticles is a promising adsorbent for CR removal from aqueous solutions, and it is easily recycled owing to its large specific surface area and unique magnetic responsiveness.
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Rojo Congo/química , Compuestos Férricos/química , Nanopartículas de Magnetita/química , Polietilenglicoles/química , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina , Adsorción , Concentración de Iones de Hidrógeno , Cinética , Temperatura , Contaminantes Químicos del Agua/química , Purificación del AguaRESUMEN
D222G mutation of the hemagglutinin (HA) is of special interest because of its close association with the enhanced virulence of 2009 pandemic influenza A (H1N1) virus through the increased binding affinity to α2,3-linked sialylated glycan receptors. However, there is still a lack of detailed understanding about the molecular mechanism of this enhanced virulence. Here, molecular dynamics simulation and binding free energy calculation were performed to explore the altered glycan receptor binding mechanism of HA upon the D222G mutation by studying the interaction of one α2,3-linked sialylglycan (sequence: SIA-GAL-NAG) with the wild type and D222G mutated HA. The binding free energy calculation based on the molecular mechanics generalized Born surface area (MM-GBSA) method indicates that the D222G mutated HA has a much stronger binding affinity with the studied α2,3-linked glycan than the wild type. This is consistent with the experimental result. The increased binding free energy of D222G mutant mainly comes from the increased energy contribution of Gln223. The structural analysis proves that the altered electrostatic potential of receptor binding domain (RBD) and the increased flexibility of 220-loop are the essential reasons leading to the increased affinity of HA to α2,3-linked sialic acid glycans. The obtained results of this study have allowed a deeper understanding of the receptor recognition mechanism and the pathogenicity of influenza virus, which will be valuable to the structure-based inhibitors design targeting influenza virus entry process.
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Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/epidemiología , Modelos Moleculares , Mutación/genética , Pandemias , Sustitución de Aminoácidos/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Humanos , Enlace de Hidrógeno , Gripe Humana/virología , Simulación de Dinámica Molecular , Proteínas Mutantes/química , Polisacáridos/química , Polisacáridos/metabolismo , Unión Proteica , Termodinámica , Virulencia/genéticaRESUMEN
Organophosphorus (OP) esters are known to bind covalently to the active site serine of enzymes in the serine hydrolase family. It was a surprise to find that proteins with no active site serine are also covalently modified by OP. The binding site in albumin, transferrin, and tubulin was identified as tyrosine. The goal of the present work was to determine whether binding to tyrosine is a general phenomenon. Fourteen proteins were treated with a biotin-tagged organophosphorus agent called FP-biotin. The proteins were digested with trypsin and the labeled peptides enriched by binding to monomeric avidin. Peptides were purified by HPLC and fragmented by collision induced dissociation in a tandem ion trap mass spectrometer. Eight proteins were labeled and six were not. Tyrosine was labeled in human alpha-2-glycoprotein 1 zinc-binding protein (Tyr 138, Tyr 174 and Tyr 181), human kinesin 3C motor domain (Tyr 145), human keratin 1 (Tyr 230), bovine actin (Tyr 55 and Tyr 200), murine ATP synthase beta (Tyr 431), murine adenine nucleotide translocase 1 (Tyr 81), bovine chymotrypsinogen (Tyr 201) and porcine pepsin (Tyr 310). Only 1-3 tyrosines per protein were modified, suggesting that the reactive tyrosine was activated by nearby residues that facilitated ionization of the hydroxyl group of tyrosine. These results suggest that OP binding to tyrosine is a general phenomenon. It is concluded that organophosphorus-reactive proteins include not only enzymes in the serine hydrolase family, but also proteins that have no active site serine. The recognition of a new OP-binding motif to tyrosine suggests new directions to search for mechanisms of long-term effects of OP exposure. Another application is in the search for biomarkers of organophosphorus agent exposure. Previous searches have been limited to serine hydrolases. Now proteins such as albumin and keratin can be considered.