Barcode encoding

Once we have found a mixture or sublibrary that shows biological activity, how do we determine exactly which structure or stnictures are responsible for the activity We can purify and analyze as described in the previous section, but if no direct analysis is available, we need to encode or tag the support or the molecules themselves, using physical or molecular "barcodes." An obvious approach that can be used only with small libraries is to physically label each vial of one-bead one-compound resin. This may be practical for a few tens of compounds, but what if we have a library of 32,(X)0 compounds, or even 1.000,000 compounds, in a mixture Clearly, there is a need for a more automated means of identifying the. structures that arc in the library. 

Barcodes are among the best known codes for a large variety of items. Many libraries rely on barcodes for the automated storing and tracking of books, and most repositories of pharmaceutical companies use barcodes to encode their test compounds. Therefore, it is not surprising that this technique has also been used for the encoding of chemical/structural informahon during synthesis. 

Fig. 4 siRNA barcode screen. First, plasmids encoding shRNA and barcode sequences are packaged into retroviruses which are used to infect cells at a concentration of 1 virus per cell. Cells are divided and treated with different culture conditions. DNA is then extracted from selected cells and the barcode is recovered by PCR. The abundance of each barcode can be determined by hybridization to a DNA microarray containing the complement of these sequences. Finally, the shRNA in each cell group will be identified... 

Nobles, K. N., Xiao, K., Ahn, S., Shukla, A. K., Lam, C. M., Rajagopal, S., et al. (2011). Distinct phosphorylation sites on the beta 2-adrenergic receptor establish a barcode that encodes differential functions of beta -arrestin. Science Signaling, 4(185), ra51. 

A barcode basically is a machine-readable visual representation of information printed on the surface of objects. There are several different kinds of barcodes, for example, barcodes which store data in the widths and spacing of printed parallel lines, and those that store data within the patterns of dots, or concentric circles, or even hidden within images. This encoded data on the barcodes is read by barcode readers, which update the backend ERP, SCM, or WMS systems. However there are some inherent issues with using a barcode, for instance, barcodes become ineffective in rain, fog, snow, dirt and grime, and so forth (Tecstra, n.d.). Since barcodes rely on optical sensors, any minor change on the barcode print can make it difficult to read. This can be commonly seen at point of sale (POS) in the supermarkets, where the POS operator scans the barcode several times because it is either wet or not aligned properly. 

Karthikeyan M, Bender, A (2005) Encoding and Decoding Graphical Chemical Structures as Two-Dimensional (PDF417) Barcodes. J Chem Inform Model 45 572-580... 

In this approach, DNAs are tagged on small molecules and serve as barcodes to record both the structural information of the small molecules and the library information. DNA-recorded libraries, which consist of large numbers of encoded small molecules, have been generated in time- and cost-effective manner. Repeated cycles via a well-established procedure, known as spUt-and-pool synthesis strategy in combinatorial chemistry, ensure production of huge compound libraries with diversity. 

Xiang, Y, Y. Zhang, Y. Chang, Y. ChaL J. Wang, and R. Yuan. 2010. Reverse-micelle synthesis of elec-trochemically encoded quantum dot barcodes Application to electronic coding of a cancer marker. Anal. Chem. 82 1138-1141. 

Chemical libraries have been encoded by addition of a specific DNA tag, or barcode, for identification, and the use of DNA-encoded libraries has been reviewed. DNA barcodes have been used to track hematopoietic stem cells in vivo using high-throughput sequencing, in whole genome sequence analysis, and in a DNA machine that relies upon two different endonucleases. ... 

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