Bernard Green

BeatSeps Ltd.

We report a multi-step approach for the synthesis of protein-imprinted polymeric particles that selectively bind tumor necrosis factor alpha (TNFα). With high affinity for TNF-α, this type of polymer may provide a novel, safe treatment or preventive approach for addressing inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis).A ke...

Targeted Intracellular Photodynamic Therapy (TIP) is a novel advance on traditional photodynamic therapy (PDT) in which photosensitizer activation is afforded by chemiluminescence rather than by laser beam. This advance allows PDT access to target cells essentially anywhere in the body. TIP also has advantages over bioluminescence as there is no ne...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An efficient novel method for the synthesis of a covalent molecularly imprinted polymer (MIP) highly specific to β-estradiol have been developed. MIP prepared by both covalent and non covalent techniques, demonstrated high selectivity toward β-estradiol. MIPs were synthesized by radical polymerization of 17-β-estradiol 4-vinyl-benzene carboxyl or s...

Introduction Chemistry Through Crystallization Photochemical Solid-State Reactions Homogeneous Solid-State Reactions Complexes, Clathrates, and Two-Component Solids Solid-State Chemistry of Radical Pairs Asymmetric Synthesis Via Reactions in Chiral Crystals Stereochemistry and Crystal Growth

The well-known polymer, polysulfone (PS), was used, via its carboxylated derivative, as a carrier vehicle for low-molecular weight substances (haptens). The synthesis and characterization of conjugates of PS-CO2H (1) coupled to a relatively non-immunogenic aliphatic hapten (2) or an aromatic hapten (3) and various intermediates in their syntheses,...

The crystal structures of catalytic antibody D2.3 Fab with the two enantiomers, 7D and 7L, which represent transition state analogues for the hydrolysis of the corresponding esters, 6D and 6L, were determined to better understand remarkable reactivity differences: the L-ester displayed significantly tighter binding (K(M)) and increased catalytic ac...

Mustard gas (sulfur mustard, HD) is a powerful vesicant employed as a chemical weapon. The present study demonstrates the effect of povidone iodine (PI) ointment against skin toxicity caused by HD. Gross and histopathological examinations showed that application of PI 20 min or less following exposure to the vesicant resulted in marked skin protect...

UV irradiation of a solution of the pheromone 1,7-dioxaspiro[5,5]undecane (DU) and β-cyclodextrin percinnamate (β-CD-PC) induces the formation of intramolecular cyclobutane bridges that trap the pheromone within the cyclodextrin cavity. Release of the pheromone can be achieved by bond-breaking chemical reactions, suggesting that such systems may be...

The application of stereoselective antibodies in an enzyme immunoassay enables the quantitative determination of enantiomeric impurities beyond the outer limits of currently available methods; thus, using an antibody raised against a derivative of D-phenylalanine, the D-enantiomer of the free amino acid can be detected in a 100000 fold excess...

The immobilization of antibodies onto solid phases in an efficient and activity-retaining form is an important goal for both research and industry. Methods have been developed for the site-directed attachment of antibodies to agarose by oxidation of the carbohydrate moieties in their Fc region. Similar attachment to silianized supports have not bee...

In this paper we demonstrate the suitability of antibodies as tailor-made chiral selectors. Polyclonal and monoclonal antibodies which stereoselectively bind to the functional grouping of α-amino acids were raised and used for the detection and chiral separation of amino acid enantiomers. The antibodies were used in various analytical applications,...

Based on the stereoselectivity of immunoglobulins, we have developed a new chiral sensor for the detection of low-molecular-weight analytes. Using surface plasmon resonance detection, enantiomers of free, underivatized -amino acids can be monitored in a competitive assay by their interaction with antibodies specific for the chiral center of this cl...

The antibody D2.3 catalyzes the hydrolysis of several p-nitrobenzyl and p-nitrophenyl esters with significant rate enhancement; product inhibition is observed with the former compounds but not with the latter. Whereas enzyme specificity has been extensively studied by X-ray crystallography, structural data on catalytic antibodies have thus far rela...

We report structures of complexes of two esterase-like catalytic antibodies elicited against phosphonate transition-state analogues (TSAs) of the reaction they catalyse; the complexes studied are with these TSAs and species along the reaction pathway. The TSAs are deeply sequestered in a pocket located in the combining site at the interface of the...

The concept of synthesizing stable analogs of the rate-limiting transition state for a given chemical reaction and then using these substances as haptens to raise antibodies which serve as specific catalysts for that reaction, has now been demonstrated for a considerable number of reactions [1]. Although this notion dates back to Pauling [2] and wa...

The catalytic mechanisms of two esterase-like catalytic antibodies (Abs) have been determined, based on kinetic data and on structures of the complexes with transition-state analogs and with a stable substrate analog of the reactions they catalyze. Both Abs stabilize the oxyanion intermediate close to the transition state in ester hydrolysis. The d...

Immobilization of low molecular weight haptens in ELISA usually involves their coupling to protein molecules or covalent binding to the solid phase. In this study we demonstrate that it is possible to directly bind the hapten p-aminophenylalanine to gamma-irradiated polystyrene microtiter plates for the detection of antibodies that stereospecifical...

The x-ray structures of the unliganded esterase-like catalytic antibody D2.3 and its complexes with a substrate analogue and with one of the reaction products are analyzed. Together with the structure of the phosphonate transition state analogue hapten complex, these crystal structures provide a complete description of the reaction pathway. At alka...

Antibody CNJ206 catalyses the hydrolysis of p-nitrophenyl esters with significant rate enhancement; however, after a few cycles, 90% of the catalytic activity of CNJ206 is irreversibly lost. This report investigates the properties of the inactivated Fab (fragment antigen binding). After inactivation, the residual esterase activity of CNJ206 is simi...

Antibody CNJ206 catalyses the hydrolysis of p-nitrophenyl esters with significant rate enhancement; however, after a few cycles, 90% of the catalytic activity of CNJ206 is irreversibly lost. This report investigates the properties of the inactivated Fab (fragment antigen binding). After inactivation, the residual esterase activity of CNJ206 is simi...

A number of monoclonal antibodies elicited against a nitrobenzyl (Nbzl)-phosphonate transition-state analogue (TSA), and which were selected for the hydrolysis of the corresponding Nbzl-ester, were also found to catalyze the hydrolysis of the analogous p-nitrophenyl(Np) ester with notable efficiency and specificity. The activity towards the Np-este...

The x-ray structures of three esterase-like catalytic antibodies identified by screening for catalytic activity the entire hybridoma repertoire, elicited in response to a phosphonate transition state analog (TSA) hapten, were analyzed. The high resolution structures account for catalysis by transition state stabilization, and in all three antibodie...

 Mustard gas (sulphur mustard, SM) is a powerful vesicant employed as a chemical weapon. The present study demonstrates the effect of povidone iodine (PI) ointment against skin toxicity caused by SM. Gross and histopathological examinations showed that application of PI up to 20 min following exposure to the vesicant resulted in marked skin protect...

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and...

Eine kontroverse Zuordnung berichtigt wurde durch die Bestimmung der absoluten Konfiguration von (+)-Isofluran (+)−1 und (+)-Desfluran (+)−2 durch anomale Rontgendispersion bei −180 °C. Die rechtsdrehenden Isomere sind im Einklang mit mehreren anderen Befunden (S)-konfiguriert. Diese Zuordnung hat besonders fur die Beschreibung des stereochemischen...

A controversial assignment has been revisited by the determination of the absolute configurations of ( + )-isoflurane [(+)-1] and (+)-desflurane [(+)-2] by anomalous X-ray dispersion at −180°C. The dextrorotatory isomers should have the (S) configuration, in agreement with other findings. The consequences of this assignment are particularly importa...

The toxicity of two new monofunctional sulfur mustard derivatives was tested. The compounds (4-carboxybutyl 2-chloroethyl sulfide, CBCS; 10-carboxydecyl 2-chloroethyl sulfide, CDCS) possess the 2-chloroethyl sulfide moiety present in mustard gas. Exposure of guinea pig skin to CBCS resulted in a dose-related ulcerative effect. CDCS exhibitedd simil...

The x-ray structure of the complex of a catalytic antibody Fab fragment with a phosphonate transition-state analog has been determined. The antibody (CNJ206) catalyzes the hydrolysis of p-nitrophenyl esters with significant rate enhancement and substrate specificity. Comparison of this structure with that of the uncomplexed Fab fragment suggests ha...

Antibody CNJ206 catalyzes the hydrolysis of p-nitrophenyl esters with significant rate enhancement and product specificity. We report here kinetic and affinity measurements for this antibody in the pH 4-9.5 range. We also report the X-ray structures of CNJ206 Fab liganded with a transition-state analog (TSA) and with one of the products of the hydr...

Cage-type clathrate inclusion complexes of tri-o-thymotide (TOT, 2) afford partial resolution (ee = 38%) of (±)-enflurane (1) after a single crystallization step.

Upon testing the ability of several strains of mice to elicit esterolytic antibodies after immunization with a p-nitrobenzyl phosphonate hapten, we have found that the occurrence of catalytic antibodies in SJL and MRL/lpr autoimmune mice is dramatically higher than in normal mouse strains (e.g., the wild-type MRL/++ or BALB/c). Fewer than 10 cataly...

CYCLODEXTRINS and modified derivatives can bind, and sometimes modify the properties of, guest molecules in their torus-shaped cavities1,2. They have also been used as the building blocks of molecular materials and devices3. The propensity to bind and retain a guest is not easily predictable or controllable, however. There is currently much interes...

Tetranitromethane (TNM) chemically mutates the binding sites of antibodies so that the nitrated antibodies exhibit pH-dependent binding near physiological pH. Three monoclonal antibodies were selectively modified, each under different conditions, with the resultant loss of binding activity at pH > 8 which is recovered at pH < 6. Recovery and loss o...

Antibodies with catalytic properties can be prepared by eliciting an antibody response against 'transition state analog' haptens. The specificity, rate and number of reaction cycles observed with these antibodies more closely resemble the properties of enzymes than any of the many other known enzyme-mimicking systems. We have determined to 3 A reso...

A prerequisite to the design and engineering of catalytic antibodies is the knowledge of their structure and in particular which residues are involved in binding and catalysis. We compared the structure and catalytic properties of a series of six monoclonal antibodies which were all raised against a p-nitrophenyl (PNP) phosphonate and which catalyz...

In the past few years, antibodies that catalyze a variety of reactions with enzyme-like properties have been produced. The present review is of a critical nature, rather than a survey or an introduction to the field of catalytic antibodies. Here, we examine the performance of catalytic antibodies in light of the features that define an enzyme: subs...

Cyclodextrin derivatives dissolved in polysiloxanes could be used for the first time as the stationary phase in enantioselective preparative gas chromatography. The authors separated the racemates of the inhalation anesthetic enflurane which is still administered as a racemate.

We present here a newly developed approach based on DBU catalyzed transesterification of bis-PNP-phosphonates, used for the preparation of phosphonoesters and their protein conjugates. These are being used, as transition state analogs, to elicit catalytic antibodies having enzyme-like properties.

The low abundance and activity of catalytic antibodies are major obstacles to their selection from the virtually unlimited repertoire of antibody binding sites. The requirement for new screening methodologies is further emphasized by the availability of combinatorial libraries, in which a functional polypeptide has to be selected out of millions of...

DBU (1,8-diazabicyclo[5.4.0]undecene) was found to efficiently mediate the transesterification of p-nitrophenyl (PNP) phosphonates by various alcohols. The reactions of bis-PNP phosphonates in the presence of DBU, using both primary and secondary alcohols, phenols and amines, proceed rapidly and with high yield to afford the corresponding monoalkyl...

Circular dichroism and UV-vis measurements were used to study the interaction between several water-soluble metalloporphyrins and monoclonal antibodies (MABs) that were elicited against a structurally related dihydroxytin-(IV) porphyrin, 1a. Some of the MAB-metalloporphyrin complexes studied were previously shown to mimic hemoprotein-like activity,...

The production of antibodies against the highly toxic organophosphorus compound soman (GD) has been undertaken. Monoclonal antibodies were raised against two structural analogs of soman which served as haptens for immunization. In these soman analogs the chemically active P-F bond of the soman molecule was substituted by a P-OH group (which is ioni...

Halogenated trisalicylide derivatives 1-6, representing three-fold symmetric C3 “home trimmers” as well as dissymmetric C1 “mixed trimers” have been synthesized. Clathration studies indicate that these halogenated TOT analogs do not form clathrates. Reductive removal of the halogen was demonstrated for analog 2, providing a new entry to TOT-based h...

Several laboratories have now shown that monoclonal antibodies having enzyme-like properties can be generated. The generation of catalytic antibodies makes use of the same basic procedures that have been used for the generation of binding monoclonal antibodies, yet the process involves an additional crucial step: screening for catalytic activity. I...

Mono-, di-, tri-, tetra-, and pentabrominated tri-o-thymotide (TOT) analogues (3-7) and mono-, di-, tri-, and tetrabrominated tri-o-carvacrotide (TOC) analogues (9-12) were synthesized by direct bromination of TOT and TOC. Total yields of about 60% were realized from TOT or TOC. The degree of bromination of the methyl group depended upon the reacti...

Of the various approaches being studied to mimic the catalytic properties of enzymes, catalytic antibody research is advancing most rapidly and successfully; the discovery of new reactions and new catalytic antibody-producing haptenic structures continues unabated. One of the highlights of the past year was the design and synthesis of a catalytical...

In order to improve the relatively low yield (ca. 35%) previously observed in the synthesis of tri-o-thymotide (TOT, 1) from o-thymotic acid (2), the cyclodehydration was studied using a variety of conditions. The low yield is due to the formation of di-o-thymotide (DOT, 3), previously reported, and at least three other products (4-6), which appare...

A large variety and number of harmful and toxic agents are released into the environment and represent major health threats (Salkinoja-Salonen, et al., 1989). The destruction of unwanted stores of toxic substances in ways which are environmentally-safe is a problem facing all industrial nations. In addition, ingestion of toxic substances requires t...

Monoclonal antibodies were raised against a mono-p-nitrophenyl phosphonate ester to elicit catalytic antibodies capable of hydrolyzing the analogous p-nitrophenyl ester or carbonate. Potential catalytic antibody producing clones were selected, by use of a competitive inhibition assay, on the basis of their affinity for a "short" transition-state an...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

During the past two years, monoclonal antibodies with enzyme-like catalytic properties have been successfully raised. They catalyse a variety of reactions (hydrolysis of esters, amides and carbonates; bimolecular reactions; cyclization reactions; elimination reactions; asymmetric synthesis) with rate enhancements of up to 6 × 106 fold and high spec...

The motives for mimicking enzymes are twofold: 1) to gain information and deeper understanding which will be relevant to biochemical catalysis, and 2) to extend the chemistry of living organisms in order to be able to invent new reactions--reactions that enzymes either cannot perform, or can perform only with difficulty. It has taken a long time fo...

Antibodies were raised against an analogue of one of the photodimeric products [the cyclobutane (2)] resulting from irradiation of methyl p-nitrocinnamate (1); in the presence of these antibodies, irradiation of (1) led preferentially to the particular stereoisomer (2).

A new synthesis is described for the preparation of tri-o-thymotide (, TOT) and some TOT analogues. The methodology is based on the sequential coupling of appropriately substituted and protected salicylic acid monomers followed by cyclization of the deprotected open-chain trimers. A variety of protecting methodologies and coupling sequences are dis...

The emphasis in this paper is on the interpretation of physicochemical phenomena occurring in tri-ortho-thymotide (TOT) clathrates in the light of crystallographic data. Enantiomeric discrimination of guest included in the cageP3121 clathrates, first suggested by H. M. Powell, has been studied for about twenty guest molecules. Practical application...

Dichlorocyclopropanation as well as epoxidation of the 1,4-diarylbutadienes - to give the mono- and/or bisadducts according to several hindrance of large substituents as 2,6-dichlorophenyl. The bisadducts are formed preferably as - (or -) isomers.

The diene reacted with CHCl3/aq. NaOH/PTC in CH2 Cl2 unexpectedly to give a mixture of the chlorination products and . Usual chlorination with Cl2 yielded similarly , , and dependent on the amount of Cl2. The formation of as well as the reaction of to give (besides ) shows an unusual Cl-Cl-interaction.

Untersucht werden die [)ichIorcyclopropanierung und die Epoxidierung der unterschiedlich substituierten 1,4-Diarylbutadiene: (I), (IX), (XVI) und (XXI), die zu Mono- und/oder Bisaddukten führt.

Die Titelverbindung (I) (IEE,E) reagiert mit Dichlorcarben überraschend nicht unter Dichlorcyclopropanierung, sondern unter regioselektiver (,Thlorierung der Doppelbindungen [Bildung der Verbindungen (II) und (I I l)].

Aus den 2,fm-Dichlor-zimtsäureestern (I) erhält man bei der Bestrahlung über die cis-Form (II) das S-Chlor-cumarin (III).

The excited electronic states of an optically active substituted ethylene sulfide ((+)-(R,R)-2,3-dimethylthiirane, DMT) is discussed in light of vacuum-UV absorption and circular dichroism (CD) spectra and ab initio self-consistent-field calculations. Experimental and calculated excitation energies and oscillator and rotational strengths are compar...

Crystallization of tri-o-thymotide (TOT) from solutions of appropriate racemic guest species affords chiral single crystals of clathrate inclusion complexes in which the guest enantiomers are incorporated to different degrees. Channel-type complexes (space group P61) or cage-type complexes (P3121) are obtained. The extracted guest from single cryst...

On UV irradation, 2,6-dichlorocinnamic acid and its esters undergo photocyclization with elimination of the elements of HCl or RCl (R = alkyl or aryl) to yield 5-chlorocoumarin (2); amide derivatives yield the corresponding imino analogues. Low-temperature irradiation monitored by infrared and optical spectrophotometry allowed the identification of...

Clathrates and intercalates are not any more laboratory curiosities. The specific situation where a given matrix is able to include a large range of guests suggests a variety of experiments useful both in fundamental research and in applied fields: specific chemical reactions, polymerization, stabilization of unstable species, isomer and enantiomer...

Solvent etching of single crystals of hexahelicene grown from a racemic solution reveals an unusual layer-like pattern in which pure (+)- and pure (–)-layers alternate through the crystal; this arrangement results in a nearly racemic composition although the crystal is ostensibly chiral, space group P212121. Etched crystals of enantiomerically pure...

The structure and absolute configuration of the enantiomer of 4,4'-dimethylchalcone dibromide (C~THI6Br2 O) formed in excess in a gas/solid bromination reaction of a single crystal of 4,4'-dimethylchalcone have been determined at 85 K. The crystals are orthorhombic, space group P212121, with a = 35.167 (4), b = 5.544 (1), c = 7.915 (1)A, z = 4. Ref...

Tri-o-thymotide (TOT) forms channel-type and cage-type clathrate inclusion compounds with a wide variety of guest molecules. Since these clathrate crystals are chiral, any single crystal contains different amounts of enantiomeric guests. The clathrate type as well as the chiral discrimination (the preferred enclathration of one enantiomer over the...

The absolute configuration of tri--thymotide (TOT) has been determined by X-ray crystal structure determinations of two cage-type clathrate inclusion compounds (+)-TOTS·S-(+)-2-bromobutane and (−)-TOT·RR-(+)-2,3-dimethylthiirane; (+)-TOT has a propeller-like configuration

Das (+)-Enantiomer der Titelverbindung (I) bildet mit den Gastverbindungen (II)-(IV) Clathrate, in denen die (S)-(+)- bzw. (S,S)-(-)-Konfiguration bevorzugt wird und umgekehrt.

Irradiation of crystalline (+)-2,4:3,5-di-O-methylene-D-mannitol 1,6-di-trans-cinnamate (1) induces intermolecular cyclobutane formation leading to chiral oligomers of increasing length. The dimer, trimer, tetramer, and pentamer have been isolated and characterized. The intramolecular distance between the olefinic residues within the molecules of 1...

The circular dichroic and absorption spectra of a substituted ethylene oxide have been measured in the spectral region of 185–150 nm, the former revealing a transition that is not observed in the gas-phase absorption spectrum of ethylene oxide or a derivative.

New clathrate inclusion complexes of tri-o-thymotide (TOT) which contain cis-stilbene or trans-stilbene have been prepared and characterized; both crystallize in the triclinic space group P1 and have closely similar cell constants. Each unit cell of the trans-stilbene·TOT complex contains four TOT molecules and two stilbene molecules; the stilbenes...

The fluorescence of trans-stilbene is quenched by several electron-poor alkenes. Quenching by dimethyl fumarate and fumaronitrile is accompanied by the appearance of exciplex fluorescence in nonpolar solvents. Quenching constants increase with increasing alkene electron affinity, indicating that singlet stilbene acts as an electron donor in exciple...