Enzymatic Generation and In Situ Screening of a Dynamic Combinatorial Library of Sialic Acid Analogues

Lins, Roger J.; Flitsch, Sabine L.; Turner, Nicholas J.; Irving, Ed; Brown, Stuart A.

doi:10.1002/1521-3773(20020916)41:18<3405::aid-anie3405>3.0.co;2-p

Cited by 46 publications

(18 citation statements)

References 6 publications

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“…Enzyme-Mediated Reversible Aldol Reaction a a a-and e-denote axial and equatorial substituents, respectively. 88,89 formed in the reaction by distillation. So far, only gem-diols have been used as a masked carbonyl functionality for imine exchange.…”

Section: Cdn Exchangementioning

confidence: 99%

“…Some special approaches that nevertheless combine hydrazone chemistry and biological targets will be discussed in section 6. Finally, thioester exchange 99,100 and enzymatic reactions such as the exchange of peptidic bonds 23 and aldol reactions 88,89 are also compatible with biological targets, although thus far only two enzymes have actually been used for generating DCLs.…”

Section: Ligands For Biomoleculesmentioning

confidence: 99%

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Dynamic Combinatorial Chemistry

et al. 2006

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Section: Cdn Exchangementioning

confidence: 99%

Section: Ligands For Biomoleculesmentioning

confidence: 99%

Dynamic Combinatorial Chemistry

et al. 2006

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“…Each of them has its own characteristics, advantages and drawbacks. For the construction of DCLs in the presence of a biological target imine, acylhydrazone formation [13,[22][23][24][25][26][27][28][29], disulfide exchange [30][31][32][33], transamidation [34], transthioesterification [35], enzyme-catalyzed aldol reaction [36,37], cross-metathesis [38,39] and boronate transesterification [40] have been reported. The C=N bond formation processes, by condensation of an amino group with carbonyl functionalities, are (besides disulfide exchange) the most important class of DCC reactions and have proven to be efficient when biological systems are targeted.…”

Section: Generation Of Diversity: DCC Reactions and Building Blocksmentioning

confidence: 99%

“…Another plant lectine, wheat germ aglutidinin (WGA), was chosen as a molecular target to explore enzyme-catalyzed aldol reactions for the generation of DCLs [36,37]. Three different carbohydrate building blocks were mixed with an excess pyruvate in the presents of NANA aldolase (Fig.…”

Section: Receptor Proteins As Targetsmentioning

confidence: 99%

Dynamic Combinatorial Diversity in Drug Discovery

Hochgürtel¹,

Lehn

2006

Methods and Principles in Medicinal Chemistry

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IntroductionCombinatorial chemistry evolved as a key technology for the rapid generation of large populations of structurally distinct molecules that can be screened efficiently en masse for desirable properties. This approach, in combination with highthroughput screening, evolved into a powerful technique capable of significantly accelerating the drug discovery process [1]. Initially developed to produce peptide libraries for screening against antibodies or receptors, combinatorial synthesis and the screening of combinatorial arrays became an integral part in lead generation and optimization in drug discovery [2][3][4][5]. Furthermore, combinatorial methodologies also demonstrated their potential in other areas, such as the development and discovery of catalysts, and material science [6,7].Modern combinatorial libraries are characterized by the generation of numerous different, but structurally related compounds that exist discretely as static entities, under similar conditions, in a systematic manner. Currently, there are several distinct methodologies for the generation of combinatorial libraries [8,9]. These combinatorial arrays can be produced in a parallel fashion, either as a library of individual compounds or as pooled mixtures. In applying a parallel format, the compounds are handled individually in separated compartments. This removes difficulties associated with compound mixtures; and it allows for every individual compound a straightforward evaluation of chemical integrity and structure-activity relationship after biological testing. The library size handled with this methodology is more limited than in a pooling strategy. Pooled mixture formation is straightforward and less time-consuming than the synthesis of individual compounds. More difficult is the analysis and screening of mixtures of components. By the split and mix technology, very large libraries can be formed progressively over multiple synthetic steps. Also, several technological advances in solid phase automated synthesis, analysis, robotics and miniaturization allow the rapid parallel synthesis and characterization of very large arrays of individual compounds. The substances generated are then subsequently evaluated for biological activity by high-throughput screening, applying fully automated systems towards a chosen target protein. 341Fragment-based Approaches in Drug Discovery. Edited

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“…[6][7][8][9][10][11] A growing number of groups have shown the general applicability and scope of tdDCC for the identification of modulators of targets. [6,[12][13][14][15][16][17][18][19][20] tdDCC refers to general pharmacologically relevant targets which next to pro-tions report the use of DCC on biologically relevant target proteins. This minireview complements previous reviews by focusing on the experimental protocol and giving detailed examples of essential steps and factors that need to be considered, such as protein stability, buffer composition and cosolvents.…”

Section: Introductionmentioning

confidence: 99%

Protein‐Templated Dynamic Combinatorial Chemistry: Brief Overview and Experimental Protocol

2019

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Dynamic combinatorial chemistry (DCC) is a powerful tool to identify bioactive compounds. This efficient technique allows the target to select its own binders and circumvents the need for synthesis and biochemical evaluation of all individual derivatives. An ever‐increasing number of publications report the use of DCC on biologically relevant target proteins. This minireview complements previous reviews by focusing on the experimental protocol and giving detailed examples of essential steps and factors that need to be considered, such as protein stability, buffer composition and cosolvents.

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Enzymatic Generation and In Situ Screening of a Dynamic Combinatorial Library of Sialic Acid Analogues

Cited by 46 publications

References 6 publications

Dynamic Combinatorial Chemistry

Dynamic Combinatorial Chemistry

Dynamic Combinatorial Diversity in Drug Discovery

Protein‐Templated Dynamic Combinatorial Chemistry: Brief Overview and Experimental Protocol

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