Small molecule microarrays: recent advances and applications

Uttamchandani, Mahesh; Walsh, Daniel P.; Yao, Shao Q.; Chang, Young‐Tae

doi:10.1016/j.cbpa.2004.12.005

Cited by 120 publications

(73 citation statements)

References 48 publications

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“…The last few years have seen tremendous progress in the development of new technologies that combine combinatorial chemistry and array fabrication methods for the site-specific immobilization of up to several thousand peptides and small molecules on a single solid substrate (see refs 79 and 80 for reviews). The most widely investigated applications of small molecule microarrays have been for the identifying of protein-binding ligands and function inhibitors, while peptide arrays have been mostly utilized for screening the substrate preferences of various proteinmodifying enzymes.…”

Section: Iii3 Peptide and Small Molecule Microarraysmentioning

confidence: 99%

Microarray methods for protein biomarker detection

Lee

Wark

Corn

2008

Analyst

137

108

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The application of protein biomarkers as an aid for the detection and treatment of diseases has been subject to intensified interest in recent years. The quantitative assaying of protein biomarkers in easily obtainable biological fluids such as serum and urine offers the opportunity to improve patient care via earlier and more accurate diagnoses in a convenient, non-invasive manner as well as providing a potential route towards more individually targeted treatment. Essential to achieving progress in biomarker technology is the ability to screen large numbers of proteins simultaneously in a single experiment with high sensitivity and selectivity. In this article, we highlight recent progress in the use of microarrays for high-throughput biomarker profiling and discuss some of the challenges associated with these efforts. I IntroductionThe discovery of protein biomarkers whose change in expression level or state correlates with the progression of a disease is becoming increasingly important. Once validated, proposed biomarkers can be involved in achieving an earlier diagnosis, differentiating between disease types with greater accuracy, and assessing response to treatment. Prominent examples of biomarkers include proteins that are associated with a variety of cancers, 1-4 as well as heart, 5,6 renal, 7,8 andAlzheimer's 9,10 diseases.Most biomarker studies reported to date have focused on serum-, plasmaand urine-based samples. A number of other possibilities include saliva, tears, breath condensates, cerebrospinal fluid and tissue lysates extracted from biopsy samples. There are several excellent reviews detailing biomarker discovery and validation. [11][12][13][14][15] The potential benefits of biomarkers have greatly motivated both academic and industry researchers to apply new proteomic technologies for biomarker discovery and to develop quantitative analytical methodologies for rapid and sensitive biomarker detection. Many clinically relevant biomarkers reside in blood at picomolar concentrations and lower, which is five to seven orders of magnitude lower than the most abundant plasma proteins. Therefore, protein detection with high specificity and sensitivity is required; unfortunately, no universal ultrasensitive enzymatic amplification method (such as PCR for the case of nucleic acid detection) exists for proteins. Additionally, it is desirable to screen multiple proteins simultaneously in a single sample. Multiplexed measurements are attractive not only for economic reasons but also for identifying characteristic signal patterns associated with the relative changes in entire sets of proteins as this will provide much more insight and diagnostic accuracy than individual biomarker measurements.hyejinlee@knu.ac.kr. 14,19,[24][25][26][27][28][29][30] Although microarray methods are wellestablished for high-throughput nucleic acid studies, their application for protein detection has been limited by issues such as the surface immobilization of protein capture probes without loss in bioactivity as well a...

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Section: Iii3 Peptide and Small Molecule Microarraysmentioning

confidence: 99%

Microarray methods for protein biomarker detection

Lee

Wark

Corn

2008

Analyst

137

108

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“…1,2 There are a number of techniques for DNA immobilization. Among them, oligonucleotide immobilization on a Au surface 3,4 and on the surfaces of nanoparticles 57 has been widely pursued because of simplicity in preparation.…”

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confidence: 99%

DNA Morphologic Changes Induced by Spermine on a Gold Surface under DNA Crowding Conditions

Kobayashi¹,

Tateishi‐Karimata²,

Tsutsui³

et al. 2011

Chemistry Letters

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DNA immobilized on a gold surface was globule in the absence of spermine. Upon addition of spermine, the DNA underwent a structural transition that was dependent on DNA length from a globular structure to a random coil. This effect was opposite the DNA morphologic changes observed in dilute solutions.The conformation of DNA immobilized on a surface is of relevance to research in biotechnology and nanotechnology. 1,2 There are a number of techniques for DNA immobilization. Among them, oligonucleotide immobilization on a Au surface 3,4 and on the surfaces of nanoparticles 57 has been widely pursued because of simplicity in preparation. Recently, DNA immobilized on a solid support system has been employed in the sequencing of genes or mRNAs. 8,9 It has already been reported that oligonucleotide length affects immobilization 10 and enzymatic reactions with DNA on a surface affected by the density and structure of the DNA. Generally, high density suppresses enzymatic activities. 1113In biological systems, the density and higher-order structures of genomic DNA are important in the regulation of transcription. Genomic DNAs exist as mesoscopic-sized aggregates with histone proteins, called chromatin, and structural changes in chromatin control gene expression.14 Recently, it was suggested that higher-order structure of chromatin is affected by its density. 15 To duplicate DNA conditions in the nucleus in vitro, the preparation of high-concentration DNA solution is needed, although it is difficult because of the high cost and low solubility of long DNA. For the investigation of DNA behavior at high density, the surface immobilization of DNA is useful, since biomolecules can be accummulated on a surface. Thus, the control of the density and higher-order structure of DNA on a surface is crucial in both artificial and biological systems.Here we report morphologic changes in double-stranded DNAs of different lengths immobilized on a Au surface via thiolAu bonds. Five different lengths of DNA were employed: 500, 1000, 2000, 3110, and 5000 bp. DNA length effects on the immobilization behavior and morphology of DNA were investigated under various salt conditions of the supernatant solution.DNA immobilization to the Au surface was performed according to previously reported procedures.3,4 Thiolated DNAs were prepared by PCR using -DNA as a template (see Supporting Information 31 ). Thiolated DNA solution (10 nM) was allowed to stand on the Au substrate for various time periods. The substrate was washed with ultrapure water and was then immersed in 1.0 mM 11-sulfanylundecanol for 1 h. During this time, a self-assembled monolayer (SAM) formed and nonspecifically bound DNA was removed. Amounts of immobilized DNA were quantified by SYBR Gold (Invitrogen) staining with fluorescence measured using FLA 7400 (FujiFilm Co., Ltd.). Until SAM formation, no fluorescence from SYBR Gold modified DNA was observed because of quenching by Au. Treatment with 1.0 mM 11-sulfanylundecanol results in SAM formation, and fluorescence was observed as the...

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“…To date, only a few of these slide surfaces are commercially available. Slides of type 2 B-D are recommended for immobilization of small molecules such as short peptides, oligonucleotides, monosaccharides and other low molecular weight compounds [32], due to various distance dependant surface effects. First, there is an effect of decreased diffusion rate constant near surfaces leading to reduced rates of molecular recognition [33,34].…”

Section: Molecular Architecturementioning

confidence: 99%

Microarray Technology as a Universal Tool for High-Throughput Analysis of Biological Systems

Sobek¹,

Bartscherer²,

Jacob³

et al. 2006

CCHTS

110

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Over the last years microarray technology has become one of the principal platform technologies for the highthroughput analysis of biological systems. Starting with the construction of first DNA microarrays in the 1990s, microarray technology has flourished in the last years and many different new formats have been developed. Peptide and protein microarrays are now applied for the elucidation of interaction partners, modification sites and enzyme substrates. Antibody microarrays are envisaged to be of high importance for the high-throughput determination of protein abundances in translational profiling approaches. First cell microarrays have been constructed to transform microarray technology from an in vitro technology to an in vivo functional analysis tool. All of these approaches share a common prerequisite: the solid support on which they are generated. The demands on this solid support are thereby as manifold as the applications themselves. This review is aimed to display the recent developments in surface chemistry and derivatization, and to summarize the latest developments in the different application areas of microarray technology.

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Small molecule microarrays: recent advances and applications

Cited by 120 publications

References 48 publications

Microarray methods for protein biomarker detection

Microarray methods for protein biomarker detection

DNA Morphologic Changes Induced by Spermine on a Gold Surface under DNA Crowding Conditions

Microarray Technology as a Universal Tool for High-Throughput Analysis of Biological Systems

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