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Biomedical subjects

Bing Yan

Publications and source records attributed to Bing Yan.

At least 37 records · Page 2Linked to original sources

Compound transfer efficiency from polystyrene surfaces: application to microarrayed compound screening.

In microarrayed compound screening (microARCS), compounds are spotted and dried onto a polystyrene sheet (ChemCard)ata high density and introduced into the assay by contacting with agarose gels that contain reagents for the assay. The authors have conducted studies to characterize the compound transfer process using 59 compounds of diverse properties. The amount of compounds remaining on the ChemCard was determined by liquid chromatography/mass spectrometry after incubation with agarose gels for predetermined time periods. The results showed good correlation with kinetics of compound transfer to phosphate-buffered saline (PBS) buffer, but only moderate correlation with equilibrium solubility of compounds in PBS buffer. These observations indicate that the major factor determining compound transfer efficiency is the kinetics of dissolution of compounds, rather than equilibrium solubility and diffusion of compounds in the gel. Compounds of lower ClogP showed a higher rate of transfer to agarose gels and vice versa. Other compound properties such as molecular weight, size, acid-base, and H-bonding properties did not significantly affect compound transfer. Importantly, the majority of the compounds studied show greater than 20% transfer after a 10-min incubation with agarose gels, providing sufficient amounts of compounds for screening purposes.

Chromatography, High Pressure Liquid↗

[Clinical value of ultrasound guided transperineal prostate biopsy in detecting prostate cancer].

OBJECTIVE: To report our experience of ultrasound guided transperineal 6-core prostate biopsy (UG6CPB) in the diagnosis of prostate cancer (PCa). METHODS: In a prospective study, we performed UG6CPB in 104 suspected PCa patients with tPSA more than 4 microg/L and analysed the positive rate and complications of the diagnostic approach. RESULTS: PCa was detected in 24 of the 104 patients (23%), with low grade Gleason 2 to 4 in 3 cases (12.5%), intermediate grade Gleason 5 to 7 in 15 (62.5%) and high grade Gleason 8 to 10 in the remaining 6 (25%). Complications included temporary hematuria in 5 patients (4.8%), mild postbiopsy perineal discomfort in 5 (4.8%) and fever in 4 (3.8%). TPSA > or =10 microg/L, fPSA > or = 2 microg/L, fPSA/tPSA < 0.16, PSAD > or = 0.2 and prostate volume < 40 ml were the significant influencing factors of biopsy positive rate (P < 0.05). CONCLUSION: UG6CPB is an exact and a safe way of detecting PCa.

Biopsy, Needle↗

Spectroscopic study on the photophysical properties of lanthanide complexes with 2, 2'-bipyridine-N, N'-dioxide.

Five novel lanthanide (Eu3+, Tb3+, Gd3+, Sm3+ and Dy3+) complexes with 2, 2'-bipyridine-N, N'-dioxide (bipyO2) were synthesized and characterized by elemental analysis, IR spectrum. The triplet state energy of bipy O2 was determined to be 22275 cm(-1) with the phosphorescence spectrum of bipy O2 and its gadolinium complex. The photophysical properties of these complexes indicated that the triplet state energy of the ligand is suitable for the sensitization of the luminescence of Eu3+, Tb3+, Sm3+ and Dy3+, especially of Tb3+.

2,2'-Dipyridyl↗

[Soluble expression and target study to brain of anti-TfR ScFv].

The single-chain antibody gene (ox26-scFv) to transferrin receptor (TfR) was synthesized and amplified by three-step PCR. After sequencing, the gene was cloned into prokaryotic expression vector pTIG-Trx which carried thioredoxin (Trx) gene and a C-terminal His.tag. The Ox26-scFv proteins achieved 31% yields of total bacteria proteins at 20 degrees C, after 0.02mM IPTG induction using the strain E. coli BL21 (DE3). The soluble scFv proteins in cytoplasm suspension were about 35% and the inclusion bodies were about 65%. The soluble products were purified by immobilized metal chelation affinity chromatography (Ni-NTA), a single band with molecular weight 29 kD appeared on SDS-PAGE gel. Rat GH3 cell immunocytochemistry staining showed that Ox26-scFv protein could recognize and bind to transferrin receptor. Injected SD rats with Ox26-scFv proteins by tail veins, the antibodies were detected from brain tissues specially on the brain capillaries 4 h later which indicate that Ox26-scFv proteins have a good target function to brain capillaries and can permeate the blood-brain barrier mediated by the transferrin receptors.

Animals↗

Parallel high-throughput accurate mass measurement using a nine-channel multiplexed electrospray liquid chromatography ultraviolet time-of-flight mass spectrometry system.

A nine-channel multiplexed electrospray (MUX) liquid chromatography ultraviolet time-of-flight mass spectrometry (LC/UV/TOFMS) system has been used to simultaneously measure accurate masses of eluting components from eight parallel gradient LC columns. Accuracies better than 5 and 10 ppm were achieved for 50 and 80% of samples, respectively, from a single batch analysis of ten plates (960 samples) of a Fmoc-Asp(OtBu)-OH and reserpine mixture. Combinatorial library compounds were analyzed using this parallel high-throughput system in both positive and negative modes to rigorously verify expected products and identify side products. A mass accuracy of 10 ppm root mean square (RMS) is routinely obtained for combinatorial library samples from this high-throughput accurate mass LC/MS system followed by automated data processing. This mass accuracy is critical in revealing combinatorial synthesis problems that would be missed by unit mass measurement.

Alanine↗

High-throughput liquid chromatography ultraviolet/mass spectrometric analysis of combinatorial libraries using an eight-channel multiplexed electrospray time-of-flight mass spectrometer.

We report a high-throughput liquid chromatography/mass spectrometry (LC/MS) protocol for analyzing large combinatorial libraries using an eight-channel parallel LC/UV/MS (MUX-LCT) system. System configuration, linear response range in UV absorbance, LC column selection, and flow rate were optimized for 24 h/7 day unattended operations. Combinatorial libraries were analyzed on this system at a rate of 3200 compounds per day for a 3.5 min cycle time per injection. This parallel system is compared with a single-channel system in terms of performance and operation.

Journal Article↗

Single-bead analysis in combinatorial chemistry.

Notable limitations have previously prevented the wide application of split synthesis. However, recent developments in highly condensed and miniaturized biological screening and single-bead analysis methods have argued for a revival of split combinatorial synthesis. Although there are still many challenges, we are now in a much better position to accomplish high-throughput analysis and screening of one-bead-one-compound libraries.

Combinatorial Chemistry Techniques↗

[Refractivity of C60 composite material].

The experiment makes C60 composite material by mixing up C60 and polymethyl methacrylate. Then three minor studies are conducted: (1) Studying the relation of refractivity of the material with the change in temperature. (2) Studying the different change in refractivity with different amount of C60 in the composite material. (3) Studying the change in refractivity of the material radiated with ultraviolet radiation. A comparison is made between the above three cases. The result shows that: under different circumstances, the change in refractivity with the change of temperature differ.

Chemical Phenomena↗

Crucial Factors Regulating Site Interactions in Resin Supports Determined by Single Bead IR.

Interactions between resin-bond reactive groups were determined by measuring the single bead IR signals sensitive to their association and dissociation. Our results strongly indicate that site separation and site interaction always occur and that they are in a dynamic equilibrium in resins. The highly dynamic nature of the site interaction was demonstrated by the lack of linker-length influence on site interaction. An increased competition for nearby sites or a reduced availability of the nearby sites all suppressed site interaction, indicating the importance of the availability of sites. Our results indicated that the less bulky microenvironment, the more reactive functional group, and the more available nearby sites are factors which favor site interaction.

Journal Article↗

Real-Time Monitoring of the Catalytic Oxidation of Alcohols to Aldehydes and Ketones on Resin Support by Single-Bead Fourier Transform Infrared Microspectroscopy.

Catalytic oxidations of primary, benzylic, and secondary alcohols to aldehydes and ketone using tetra-n-propylammonium perruthenate (TPAP) were carried out on resin supports for the first time. The reaction time course, percent conversion, and influence of catalyst amount have been determined by analyzing IR spectra taken directly on a single resin bead in real time. Using 0.2 equiv of TPAP, a 92-97% conversion of alcohol to aldehyde or ketone has been achieved in 0.7-4 h based on the rates (rate constants (1.9 x 10(-)(4))-(2.5 x 10(-)(3)) s(-)(1)) of disappearance and appearance of IR bands characteristic for alcohol, aldehyde, and ketone. The rapid adaptation of this oxidation method for solid-phase synthesis demonstrates that single-bead FTIR microspectroscopy is a powerful method for facilitating the time-consuming reaction optimization stage of combinatorial chemistry.

Journal Article↗

Progression of Organic Reactions on Resin Supports Monitored by Single Bead FTIR Microspectroscopy.

We report the time courses of five solid-phase reactions obtained using single bead FTIR microspectroscopy. This time-resolved information aided in the determination of the required reaction time, the nature of the solid-phase reaction, and resin property, effectively assisting in the initial phase of our combinatorial chemistry efforts. Our results showed that solid-phase organic reactions proceed faster than generally speculated. In addition, we have shown that reactions on the surface and in the interior of the bead occur at the same rate for reactions studied. The reaction on the TentaGel resin was shown to be not faster than reactions on Wang resin, suggesting that the diffusion of the substrate into polystyrene bead copolymerized with 1% divinylbenzene is not rate-limiting. Finally, the capability of obtaining IR spectra from the partial surface of a single bead demonstrated the femtomolar detection limit of single bead FTIR microspectroscopy.

Journal Article↗

Color test for the detection of resin-bound aldehyde in solid-phase combinatorial synthesis.

We report the development of a sensitive and specific color test for the detection of the presence of resin-bound aldehyde groups using 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald). Aldehyde resin turns dark-brown to purple after a 5 min reaction followed by a 10 min air oxidation period. Resins that possess other functional groups (i.e., ketone, ester, amide, alcohol, and carboxylic acid) do not change color under the same conditions. The detection limit is 20 micromol/g for polystyrene-based aldehyde resins.

Journal Article↗

Kinetics study of amine cleavage reactions of various resin-bound thiophenol esters from marshall linker.

The kinetics of cleavage reactions of seven resin-bound thiophenol esters with three amines has been studied by single-bead FTIR. The reactivity of these seven thiophenol esters was dependent on their structures and could be summarized as follows: 5-benzimidazolecarboxylic thiophenol ester > alkyl thiophenol ester > aromatic thiophenol ester. The reactivity of three amines was summarized as follows: n-butylamine > 3,4-dimethoxyphenethylamine > 1-piperonylpiperazine. The rate of the cleavage reaction increased 2-fold per 10 degrees C rise in reaction temperature. Oxidation of the thiophenol linker increased the rate of the cleavage reaction by 580-fold.

Journal Article↗

Quality control in combinatorial chemistry: determination of the quantity, purity, and quantitative purity of compounds in combinatorial libraries.

The quality of combinatorial libraries determines the success of biological screening in drug discovery programs. In this paper, we evaluate and compare various methods for measuring identity, purity, and quantity (yield) of combinatorial libraries. Determination of quantitative purity reveals the true library quality and often indicates potential quality problems before full-scale library production. The relative purity can be determined for every member in a large library in a high-throughput mode, but must be cautiously interpreted. In particular, many impurities are not observable by relative purity measurements using detectors such as UV(214), UV(254), and evaporative light-scattering detection. These "invisible" impurities may constitute a significant portion of the sample weight. We found that TFA, plastic extracts, inorganic compounds, and resin washout are among these impurities. With compelling evidence, we reach a conclusion that purification is the only way to remove "invisible" impurities and improve the quantitative purity of any compound even though some compounds may have a high relative purity before purification.

Combinatorial Chemistry Techniques↗

High-throughput purification of combinatorial libraries I: a high-throughput purification system using an accelerated retention window approach.

We have developed a high-throughput purification system to purify combinatorial libraries at a 50-100-mg scale with a throughput of 250 samples/instrument/day. We applied an accelerated retention window method to shorten the purification time and targeted one fraction per injection to simplify data tracking, lower QC workload, and simplify the postpurification processing. First, we determined the accurate retention time and peak height for all compounds using an eight-channel parallel LC/UV/MS system, and calculated the specific preparative HPLC conditions for individual compounds. The preparative HPLC conditions include the compound-specific gradient segment for individual compounds with a fixed gradient slope and the compound-specific UV or ELSD threshold for triggering a fraction collection device. A unique solvent composition or solvent strength was programmed for each compound in the preparative HPLC in order to elute all compounds at the same target time. Considering the possible deviation of the predicted retention time, a 1-min window around the target time was set to collect peaks above a threshold based on UV or ELSD detection. Dual column preparative instruments were used to maximize throughput. We have purified more than 500 000 druglike compounds using this system in the past 3 years. We report various components of this high-throughput purification system and some of our purification results.

Journal Article↗

High-throughput purification of combinatorial libraries II: Automated separation of single diastereomers from a 4-amido-pyrrolidone library containing intentional diastereomer pairs.

A 4-amido-pyrrolidone library that was intentionally synthesized as pairs of diastereomers was produced by solution-phase parallel syntheses and purified by an automated high-throughput purification system. A total of 2592 4-amido-pyrrolidinones were ultimately isolated as single diastereomers from a matrix of 1920 syntheses. After the four-step synthesis and HPLC purification, the average yield of a single diastereomer was 36.6%. The average chemical purity was >90%, and the average diastereomeric purity was >87%. The choice of chiral amines used to make amides with heterocyclic acid chlorides had a dramatic effect on success. Analysis of the relationship between amines used for synthesis and the diastereomeric separation showed that amides made from chiral 1,2-amino alcohols gave superior separation to amides from chiral morpholines. The presence of a hydrogen bond donor on the amide side chain seems to be required for a better diastereomeric separation.

Journal Article↗