Peer Reviewed: High-Throughput Characterization of Combinatorial Libraries Generated by Parallel Synthesis

Kyranos, James N.; Hogan, Joseph C.

doi:10.1021/ac981874v

Cited by 65 publications

(48 citation statements)

References 23 publications

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“…Various new technologies have been utilized to increase the speed and improve the efficiency of drug discovery and development [6 -11]. High-throughput analyses are desired for rapid screening of numerous samples generated by modern synthesis and combinatorial libraries, particularly in drug discovery [2,3,12]. With an increase in the number of drug candidates, the demand to improve the productivity of analyses in pharmaceutical development has significantly raised the level of interest in high-speed LC.…”

Section: Introductionmentioning

confidence: 99%

Fundamental and practical aspects of ultrahigh pressure liquid chromatography for fast separations

Clausen

2007

J of Separation Science

161

115

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The ongoing development of HPLC has been focused on increasing the speed and efficiency of separations over the past decade. The advances in separation speed have been primarily related to the development of column technology and instrumentation. Relatively short columns packed with sub-2 microm particles provide high-speed separations while maintaining or increasing resolution. Ultrahigh pressure pump systems have been developed to overcome the high-pressure drop generated by such sub-2 microm packings. In this review, fundamental and practical aspects of ultrahigh pressure or ultrahigh performance liquid chromatography (U-HPLC) are discussed. Applications of fast U-HPLC separations are also presented.

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Section: Introductionmentioning

confidence: 99%

Fundamental and practical aspects of ultrahigh pressure liquid chromatography for fast separations

Clausen

2007

J of Separation Science

161

115

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“…In addition, mass spectrometry provides a universal means to characterize and distinguish drugs based on both molecular mass and structural features while at the same time providing high throughput. With the development of routine LC-MS interfaces and ionization techniques such as electrospray and APCI, mass spectrometry has also become an ideal HPLC detector for the analysis of combinatorial libraries [11], and LC-MS, MS-MS, and LC-MS-MS have become fundamental tools in the analysis of combinatorial libraries and subsequent drug development studies [12][13][14].…”

Section: Current Trends and Recent Developmentsmentioning

confidence: 99%

Mass Spectrometry and Drug Discovery

Breemen

Newsome

Dahl

2010

Burger's Medicinal Chemistry and Drug Discovery

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In the twenty‐first century, medicinal chemists are producing large numbers of organic compounds through a process called combinatorial chemistry and then testing them against pharmacological targets such as enzymes or receptors using high‐throughput screening. As a result, lead compounds can emerge from drug discovery programs in a few weeks instead of several years. Although a variety of spectroscopic and chromatographic techniques are used to support drug discovery, only HPLC or UHPLC combined with mass spectrometry (LC‐MS) are compatible with virtually all drug‐like molecules. In addition to providing a universal means to characterize drug molecules based on molecular mass and structural features, mass spectrometry provides high throughput. With the development of routine LC‐MS interfaces and ionization techniques such as electrospray and atmospheric pressure chemical ionization, mass spectrometry has also become an ideal HPLC detector for the analysis of combinatorial libraries. Furthermore, a variety of mass spectrometry‐based screening assays have been developed to screen complex mixtures of compounds including natural product extracts as a means of expanding the molecular diversity of drug leads. The use of mass spectrometry in support of combinatorial library synthesis and purification is addressed as well as screening applications such as frontal affinity chromatography‐mass spectrometry, gel permeation chromatography‐LC‐MS, affinity chromatography‐mass spectrometry, and pulsed ultrafiltration mass spectrometry. Since drug development issues such as metabolic stability and the formation of reactive metabolites are now being considered during the drug discovery process, some applications of mass spectrometry to early drug development are addressed.

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“…In addition, mass spectrometry provides a universal means to characterize and distinguish drugs based on both molecular weight and structural features while at the same time providing high throughput. With the development of routine LC-MS interfaces and ionization techniques such as electrospray and atmospheric pressure chemical ionization (APCI), mass spectrometry has also become an ideal HPLC detector [4]. Electrospray and APCI mass spectrometry, LC-MS, tandem mass spectrometry (MS-MS), and LC-MS-MS have become fundamental tools in the analysis of combinatorial libraries and subsequent drug development studies [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Analysis and screening of combinatorial libraries using mass spectrometry

Shin

Breemen

2001

Biopharm & Drug Disp

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Mass spectrometry is a highly selective and high throughput analytical technique that is ideally suited for the identification and purity determination of large numbers of compounds prepared using combinatorial chemistry or for the dereplication of natural products. Compounds may be characterized based on molecular weight, elemental composition and structural features based on fragmentation patterns. When coupled to a separation technique such as highperformance liquid chromatography (HPLC) or capillary electrophoresis, mass spectrometric applications may be expanded to include analysis of complex mixtures. However, the slower speed of the separation step reduces the throughput of the analysis. This review concerns the application of mass spectrometry to the characterization of combinatorial libraries and the screening of library and natural product mixtures. Strategies to enhance the throughput of LC-MS are discussed including fast HPLC and parallel LC-MS. Also, mass spectrometry-based screening methods are described including frontal affinity chromatography-mass spectrometry, gel permeation chromatography LC-MS, direct electrospray mass spectrometry of receptor-ligand complexes, affinity chromatography-mass spectrometry, and pulsed ultrafiltration mass spectrometry.

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Peer Reviewed: High-Throughput Characterization of Combinatorial Libraries Generated by Parallel Synthesis

Cited by 65 publications

References 23 publications

Fundamental and practical aspects of ultrahigh pressure liquid chromatography for fast separations

Fundamental and practical aspects of ultrahigh pressure liquid chromatography for fast separations

Mass Spectrometry and Drug Discovery

Analysis and screening of combinatorial libraries using mass spectrometry

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