|In silico Screening for Signalosome Inhibitors|
Melanie Füllbeck, Wolfgang Dubiel, Cornelius Frömmel, Andrean Goede and Robert Preissner
The COP9 signalosome (CSN) is involved in cell cycle regulation, possesses kinase activity and is therefore an interesting therapeutic target for anti-tumor drugs. Known inhibitors of the kinase activity exhibit low binding constants. Using them a 3D similarity screening for our in-house database is performed. The superposition algorithm enables the explicit consideration of conformers reflecting the structural flexibility.
|Design and Synthesis of Novel Thiazolidine and Pyrrolidine Derivatives as DPP-IV Inhibitors |
Ramesh C. Gupta, Laxmikant Chhipa, A. B. Mandhare, Sunil S. Nadkarni, Deepa Joshi, Shital Zambad, Padmaja Pathak, Vijay C. Chauthaiwale and C. Dutt
DPP-IV inhibitors have many advantages like increasing insulin release and suppressing glucagon release in a glucose-dependent manner hence they pose less of a hypoglycemia risk and no weight gain than that observed with other antihyperglycemic agents. To develop a novel potent DPP-IV inhibitors we have synthesized and evaluated DPP-IV inhibiting activity and selectivity of various compounds. All these results would facilitate further development of Novel drugs for treatment of type 2 diabetes.
|Pharmacophore Mapping of Flavone Derivatives for Aromatase Inhibiton|
Shuchi Nagar, Md Ataul Islam, Arup Mukherjee and Achintya Saha
The study explores the structural requirements of flavones for inhibition of aromatase activity. The QSAR analysis generates the model that shows the importance of flavone ring and with molecular lipophilicity. Presence of additional aromatic ring and m-hydroxy substitution on that ring increases inhibitory activity. Space modeling study further adjudged the presence of hydrogen bond acceptor, hydrophobic and aromatic ring and critical distance among features for the inhibitory activity.
|Solid Phase Synthesis of a Fluorescent Peptide: Comparison of Fmoc-Lys(5-FAM)-Resin and Fmoc-Lys[5-FAM(Trt)-Resin|
Wenyu Fu, Ling Sheng, Anita Hong and Xiaohe Tong
We have prepared and performed comparison studies using two kinds of resins, Fmoc-Lys(5-FAM)-Rink Amide resin (I) and Fmoc-Lys[5-FAM(trt)]-Rink Amide resin (II), the latter contains a phenolic hydroxyl group protected with a trityl group. Syntheses were carried out under the same standard conditions and the peptides obtained showed no significant difference in purity. The results of these studies showed that resin (I) is adequate for synthesis of C-terminal fluorescent labeled peptide.
|EasyBeacons™ - new Probes Ideal for Realtime PCR Detection of Methylation Status of Single CpG Duplets and SNPs|
K. Skadhauge, C. Nielsen & U.B. Christensen
The EasyBeacons™ presented here are based on the novel technology Intercalating Nucleic Acid, INA®, linked to a fluorophore and a quencher. INA® is composed of normal DNA nucleotides and Intercalating Pseudo Nucleotides (IPNs). The fact that the EasyBeacons™ are mostly composed of normal DNA nucleotides means that in many respects EasyBeacons™ behave like DNA based probes, allowing use of standard buffers, primers and enzymes and hence reduces the optimisation efforts.
|Novel Fluidics Microbead Trap/Flow Cell Enhances Speed/Sensitivity of Bead-Based Bioassays Up to 5-Fold|
RM Ozanich, CJ Bruckner-Lea, JW Grate, MG Warner, BP Dockendorff, KC Antolick, HC Edberg, LH Johnson, AN Easterday
Pacific Northwest National Laboratory (PNNL) has developed a micro/nano particle trap that allows surface-functionalized magnetic or non-magnetic particles to be trapped with subsequent perfusion of sample, reagents and wash solutions, yielding significant (up to 5-fold) improvements in assay speed and sensitivity, while significantly reducing sample matrix effects.
|Indirubin inhibitors of Leishmania mexicana CRK3 Cyclin Dependent Kinase |
Dawn Taylor, Karen M. Grant and Nicholas J. Westwooda
The indirubins are known inhibitors of cyclin dependent kinases (CDKs), including CRK3 from the protozoan parasite Leishmania mexicana, which is essential for proliferation of the disease Leishmaniasis. Subsequent investigations into the pharmacological properties of the indirubins show them to be competitive ATPbinding site inhibitors of the CDKs.
|Analytical Sample Transport – A Pneumatic Solution|
Matthew Cook, Bob Lawson and Paul Martin
Pneumatic air transport systems can provide a safe, efficient and rapid means of sending samples within different departments of a research laboratory. These systems are often used within a hospital, supermarket or bank and represent an effective method for sending samples or packages to different departments. TTP LabTech has used this technology for over 6 years, predominately in our comPILER and comPOUND systems.
|Intelligent K-Means Clustering in a Multiple Endpoint Environment|
The main success of QSAR predictive technology is mainly related to the modelling of the single activity/property endpoint in chemical space. Unfortunately an optimisation of the targeted endpoint may result in losing other desired properties, for example, toxicity is increased or solubility reduced. Because of this, attempts have been made in the last few years to model chemical space against multiple endpoints.