Syntheses and Properties of Luminescent Lanthanide Chelate Labels and Labeled Haptenic Antigens for Homogeneous Immunoassays

Mikola, Heikki; Takalo, Harri; Hemmilä, Ilkka

doi:10.1021/bc00033a001

Cited by 57 publications

(26 citation statements)

References 24 publications

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“…Assays based on TRF use lanthanide chelate labels with unique fluorescence properties (24,25,33,34,55,56,58,78,79). Key among these properties is a very long fluorescence decay time and an exceptionally large Stokes' shift.…”

Section: Trf Assaysmentioning

confidence: 99%

Immunological Methods for Detection and Identification of Infectious Disease and Biological Warfare Agents

Peruski

2003

Clin Vaccine Immunol

196

119

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NATURE OF THE PROBLEMBW agents. The release of a biological weapon (BW) agent by a terrorist group or military force would likely be silent and undetectable or nearly so. As shown by anthrax attack during the fall of 2001 in the eastern United States, patients would begin appearing at hospitals and clinics within several days of exposure, most presenting with nonspecific flu-like symptoms. The first days of the outbreak might not even cause undue concern. However, depending on the type of agent and the method of dispersal, the public healthcare system would rapidly be stretched to capacity and beyond.The qualities that make a good BW agent are its relationship between aerosolization, infectivity, or toxicity and the amount of agent required to produce an effect (48). In addition, criteria such as environmental stability, ease of production, disease severity, and communicability determine which agents are the most likely to be utilized. For maximum effect, an optimal agent should be highly lethal and easily produced in large quantities and have limited options for preventive or prophylactic treatment. Given that the respiratory route is the most effective for most BW agents, stability in an aerosol form and the capability to be readily dispersed also in an aerosol (1-to 10-m particle size) are necessary. When potential agents are reviewed for these characteristics, Bacillus anthracis (anthrax) and variola major virus (smallpox) are considered to have the greatest potential for mass casualties and civil disruption. Also high on a prospective list of agents are botulinum neurotoxins, Yersinia pestis, and Francisella tularensis (48,91,92). Lower on the prospective list are Burkholderia pseudomallei and Burkholderia mallei, Rickettsia sp., Coxiella burnetii, Venezuelan equine encephalitis virus, Marburg and Ebola viruses, and influenza viruses (48,63,91,92).Emerging infectious disease agents. In addition to diseases caused by intentional epidemics, there are several emerging infectious diseases (ID) with the potential for significant public health consequences, including dengue fever, West Nile fever, and Rift Valley fever as well as the recent reemergence of malaria in the eastern United States (48,63,91,92). As with BW agents, emerging ID agents may be directly transmissible or vector borne (63). A complex interplay of factors can influence disease emergence, including genetic variation, environmental changes, and population pressures. Further compounding this already complicated situation, are the estimated 600 million international tourists annually, many with the potential to the spread disease globally in a matter of hours (63). Clearly, the challenges facing modern clinical microbiologists and immunologists are daunting enough without the added difficulties posed by the intentional release of BW/ID agents! Because of the threat posed by both BW and emerging or reemerging ID agents, there is a need to rapidly identify such agents in the clinical setting in order to treat the individuals at risk and to improve p...

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Section: Trf Assaysmentioning

confidence: 99%

Immunological Methods for Detection and Identification of Infectious Disease and Biological Warfare Agents

Peruski

2003

Clin Vaccine Immunol

196

119

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“…The structures obtained from these theoretical calculations are in very good agreement with the experimental solution structures, as demonstrated by paramagnetic NMR measurements (lanthanide-induced shifts and relaxation-rate enhancements). Data sets obtained from variable-temperature 17 O NMR at 7.05 T and variable-temperature 1 H nuclear magnetic relaxation dispersion (NMRD) on the Gd III complex were fitted simultaneously to give insight into the parameters that govern the water 1 fluencing the relaxation efficiency of the water proton nuclei in the target tissue. The efficiency of a contrast agent is evaluated in terms of its relaxivity, which is defined as the relaxation-rate enhancement of water proton nuclei per mm concentration of metal ion.…”

Section: Introductionmentioning

confidence: 99%

“…This ligand is potentially octadentate for the coordination of Ln III ions and contains pyridine units that can be easily functionalized with groups able to conjugate with biological material. [16,17] The corresponding lanthanide complexes were characterized by 1 H and 13 C NMR techniques in D 2 O solution. Luminescence studies have been carried out to test the ability of the ligand to promote a good antenna effect for Eu III and Tb III , as well as to determine the hydration number of the complexes in solution.…”

Section: Introductionmentioning

confidence: 99%

Lanthanide Chelates Containing Pyridine Units with Potential Application as Contrast Agents in Magnetic Resonance Imaging

Platas‐Iglesias

Mato‐Iglesias

Djanashvili

et al. 2004

Chemistry A European J

108

128

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A new pyridine-containing ligand, N,N'-bis(6-carboxy-2-pyridylmethyl)ethylenediamine-N,N'-diacetic acid (H(4)L), has been designed for the complexation of lanthanide ions. (1)H and (13)C NMR studies in D(2)O solutions show octadentate binding of the ligand to the Ln(III) ions through the nitrogen atoms of two amine groups, the oxygen atoms of four carboxylates, and the two nitrogen atoms of the pyridine rings. Luminescence measurements demonstrate that both Eu(III) and Tb(III) complexes are nine-coordinate, whereby a water molecule completes the Ln(III) coordination sphere. Ligand L can sensitize both the Eu(III) and Tb(III) luminescence; however, the quantum yields of the Eu(III)- and Tb(III)-centered luminescence remain modest. This is explained in terms of energy differences between the singlet and triplet states on the one hand, and between the 0-phonon transition of the triplet state and the excited metal ion states on the other. The anionic [Ln(L)(H2O)]- complexes (Ln=La, Pr, and Gd) were also characterized by theoretical calculations both in vacuo and in aqueous solution (PCM model) at the HF level by means of the 3-21G* basis set for the ligand atoms and a 46+4 f(n) effective core potential for the lanthanides. The structures obtained from these theoretical calculations are in very good agreement with the experimental solution structures, as demonstrated by paramagnetic NMR measurements (lanthanide-induced shifts and relaxation-rate enhancements). Data sets obtained from variable-temperature (17)O NMR at 7.05 T and variable-temperature (1)H nuclear magnetic relaxation dispersion (NMRD) on the Gd(III) complex were fitted simultaneously to give insight into the parameters that govern the water (1)H relaxivity. The water exchange rate (k(298)(ex)=5.0 x 10(6) s(-1)) is slightly faster than in [Gd(dota)(H2O)]- (DOTA=1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane). Fast rotation limits the relaxivity under the usual MRI conditions.

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“…Calixarene-based actinium ionophores will also have other potential biomedical applications such as contrast agents (CA) in magnetic resonance imaging (MRI) [12][13][14] and as luminescent labels for bioassay purpose (with chromophoric antenna). [15][16][17] 3. Geerlings MW, Kaspersen FM, Apostolidis C, van der Hout R. Nucl Med Commun 1993;14:121.…”

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confidence: 99%

Monofunctionalization of Calix[4]arene Tetracarboxylic Acid at the Upper Rim with Isothiocyanate Group: First Bifunctional Chelating Agent for Alpha-Emitter Ac-225

Chen

Ji²,

Fisher³

et al. 1999

Synlett

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A procedure is reported for synthesizing a novel, water-soluble bifunctional chelating agent derived from calix [4]arene. This chelate features tetracarboxylic acid groups at the lower rim as an actinium-225 ionophore, and an isothiocyanate functional group at the upper rim for labeling of the N-terminus of monoclonal antibodies through thiourea linkage.Keywords actinium-225; bifunctional chelating agents; calixarenes; isothiocyanate For radioimmunotherapy of cancer, it is well established that alpha (α) particles from radionuclide labels are more effective cytotoxic agents than beta (β) particles. This is because α particles dissipate a larger amount of energy over a shorter range (few cell diameters), and thus are more effective in cell killing than are β particles. 1,2 Among the α-emitting radionuclides considered suitable for radioimmunotherapy of cancer is actinium-225 (t 1/2 = 10 d), which decays through a rapid chain of daughter products to a stable product and emits four α particles, two β particles, and several gamma-ray (γ) photons with a combined energy of about 28 MeV. 3 Applications in radioimmunotherapy require Ac-225 to be bound to a protein that specifically targets cancer cells. This application also requires a bifunctional complexing agent that tightly binds Ac-225 on one side and can be linked to protein on the other side. This bifunctional complexing agent must be stable under physiological conditions. We have recently reported 4 that t-butylcalix [4] (2) reported in the literature. 6,7 Conversion of triacid to triester derivative was accomplished by refluxing in EtOH with catalytic amount of p-toluenesulfonic acid. Nitration was conducted with the treatment of 70% HNO 3 in the presence of HOAc at 0°C. Under these conditions, only one nitro group was introduced at the para position of the phenol ring of calix[4]arene without ester group. Further esterification of the remaining phenol group of 3 kept the tetraester in conic conformation. Hydrolysis of the mononitro-tetraester derivative, using NaOH or KOH as base, gave a mixture of free acid 4 and Na + or K + complexes. Only a bulky base, such as tetramethylammonium hydroxide (Me 4 NOH), gave a satisfactory NMR spectrum with exclusion of cation complexation. Reduction of 4 using the standard pressurized hydrogenation with Pd-C or Raney-Ni as a catalyst, gave virtually no reduction product; however, in the presence of palladized charcoal, hydrazine hydrate 8,9 reduced 4 to amine 5 in nearly-quantitative yield within 2 hours. Reaction of the amino compound with thiophosgene 10 gave the title compound, 5-isothiocyanato-25,26,27,28-tetrakis-[(hydroxycarbonyl)methoxy]-calix[4]arene (6).1 H NMR 11 of the monofunctionalized calixarene 4 clearly showed cone conformation. Because of its asymmetric structure, four pairs of doublets for the ArCH 2 Ar methylene protons (two AX systems) and 3 singlets in the ratio of 2:1:1 for OCH 2 COOH groups were found in the spectrum. Amino-and isothiocyanato-derivatives showed simplified pattern for OCH 2 COO...

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Syntheses and Properties of Luminescent Lanthanide Chelate Labels and Labeled Haptenic Antigens for Homogeneous Immunoassays

Cited by 57 publications

References 24 publications

Immunological Methods for Detection and Identification of Infectious Disease and Biological Warfare Agents

Immunological Methods for Detection and Identification of Infectious Disease and Biological Warfare Agents

Lanthanide Chelates Containing Pyridine Units with Potential Application as Contrast Agents in Magnetic Resonance Imaging

Monofunctionalization of Calix[4]arene Tetracarboxylic Acid at the Upper Rim with Isothiocyanate Group: First Bifunctional Chelating Agent for Alpha-Emitter Ac-225

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