scholarly journals The role and impact of high throughput biomimetic measurements in drug discovery

ADMET & DMPK ◽  
2018 ◽  
Vol 6 (2) ◽  
pp. 74-84 ◽  
Author(s):  
Shenaz Bunally ◽  
Robert J Young
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Drug Discovery ◽  
Physicochemical Property ◽  
Physicochemical Properties ◽  
High Throughput ◽  
High Performance ◽  
Cost Effective ◽  
High Quality ◽  
The Right

During the early phase of drug discovery, it is becoming increasingly important to acquire the full physicochemical profile of molecules. For this purpose, there is a strong interest in developing efficient and cost-effective platforms for fast and reliable measurements of physicochemical properties. We have developed an automated physchem platform which ensures that consistent, comprehensive, and high-quality physicochemical property measurements and derived property information for 100's of compounds per week are available alongside potency data at the right time to guide compound progression decisions. We discuss the routine assessments of biomimetic properties using high throughput automated high-performance liquid chromatography (HPLC) platforms, with details of the methods and hardware employed, also with illustrations of the quality and impact of the data generated.

scholarly journals Comparative Studies on the pH Dependence of DOWof Microcystin-RR and -LR Using LC-MS

2011 ◽  
Vol 11 ◽  
pp. 20-26 ◽  
Author(s):  
Gaodao Liang ◽  
Ping Xie ◽  
Jun Chen ◽  
Ting Yu
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Physicochemical Properties ◽  
Distribution Ratio ◽  
High Performance ◽  
Water Distribution ◽  
Ph Dependence ◽  
Remarkable Difference ◽  
The Difference

Microcystins (MCs) are well known worldwide as hepatotoxins produced by cyanobacteria, but little is known about the physicochemical properties of these compounds. The dependence of the n-octanol/water distribution ratio (DOW) of MC-RR and -LR to pH was measured by high-performance liquid chromatography combined with mass spectrometry (LC-MS). There was a remarkable difference in such relationships between MC-RR and -LR. The log DOWof MC-LR decreased from 1.63 at pH 1.0 to -1.26 at pH 6.5, and stabilized between -1.04 and -1.56 at a pH of 6.5~12.0; log DOWof MC-RR varied between -1.24 and -0.67 at a pH of 1.00~4.00, and stabilized between -1.20 and -1.54 at a pH of 4.00~12.00. The difference of hydrophobicity in acidic condition between MC-RR and -LR is important, not only for the analytical method of both toxins, but perhaps also for understanding the difference of toxicity to animals between the two toxins.

Application of denaturing high-performance liquid chromatography for mapping of single nucleotide polymorphisms in barley (Hordeum vulgare L.)

Genome ◽  
2001 ◽  
Vol 44 (4) ◽  
pp. 523-528 ◽  
Author(s):  
Raja Kota ◽  
Markus Wolf ◽  
Wolfgang Michalek ◽  
Andreas Graner
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Hordeum Vulgare ◽  
Dna Sequence ◽  
High Throughput ◽  
Doubled Haploid ◽  
High Performance ◽  
Nucleotide Polymorphisms ◽  
Hordeum Vulgare L ◽  
Single Nucleotide

Recent advances in DNA sequence analysis and the establishment of high-throughput assays have provided the framework for large-scale discovery and analysis of DNA sequence variation. In this context, single nucleotide polymorphisms (SNPs) are of particular interest. To initiate a systematic approach to develop an SNP map of barley (Hordeum vulgare L.), we have employed denaturing high-performance liquid chromatography (DHPLC) to analyse segregating SNP patterns in a doubled-haploid (DH) mapping population. To this end, SNPs between the parental genotypes were identified using a direct sequencing approach. Once a SNP was established between the parents, the optimal melting temperature of the PCR fragment containing the SNP was predicted for its analysis by DHPLC. Following the detection of the optimal temperature, the DH lines were analysed for the presence of either of the alleles. To test the utility of the analysis, data from previously mapped RFLP markers from which these SNPs were derived were compared. Results from these experiments indicate that DHPLC can be efficiently employed in analysing SNPs on a high-throughput scale.Key words: denaturing high performance liquid chromatography, doubled-haploid lines, restriction fragment length polymorphism, genetic mapping, molecular markers.

scholarly journals Rapid and Accurate Approach for Screening of Microsatellite Unstable Tumours Using Quasimonomorphic Mononucleotide Repeats and Denaturating High Performance Liquid Chromatography (DHPLC)

2009 ◽  
Vol 26 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Gašper Berginc ◽  
Damjan Glavač
Keyword(s):  
High Performance Liquid Chromatography ◽  
Capillary Electrophoresis ◽  
Liquid Chromatography ◽  
Microsatellite Markers ◽  
High Performance ◽  
Cost Effective ◽  
Slovenian Population ◽  
Cost Effective Approach ◽  
Msi Analysis ◽  
Colorectal Tumours

MSI analysis is becoming increasingly important for the detection of both hereditary non-polyposis colorectal cancer and sporadic primary colorectal tumours with MSI high phenotype. The Bethesda panel of five microsatellite markers has been proposed to provide uniform criteria for MSI analysis. Here we report on an MSI analysis approach using quasimonomorphic mononucleotide repeats and denaturating high performance liquid chromatography (DHPLC). We analysed 595 newly diagnosed colorectal tumours and 145 normal samples. Microsatellite markers BAT-25, BAT-26, NR-21, NR-22, and NR-27 were amplified in multiplex reaction and analysed using DHPLC and capillary electrophoresis (CE). DHPLC conditions for analysis of MSI multiplex assay were evaluated and tested. Analysis and cross-examination of the results obtained from 96 samples using DHPLC and capillary electrophoresis showed the same sensitivity and specificity of the two approaches for detecting MSI-H tumours. Using our new approach we showed that the tested markers are quasimonomorphic in a Slovenian population, with frequencies of polymorphisms 0.07%, 1.4%, 2.1%, 1.4%, and 1.4% for BAT-25, BAT-26, NR-21, NR-22, and NR-27, respectively. Forty-three (7.2%) new MSI-H tumours were identified, of which 84% showed instability in all 5 tested markers. Overall, we developed a high-throughput, robust, accurate and cost-effective approach for the detection of MSI-H tumours.

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