Deconvolution and screening

Image

Deconvolution and screening

The synthesized molecules of a combinatorial library are 'cleaved' from the solid support and mixed into solution. In such solution, millions of different compounds may be found. When this synthetic method was developed, it first seemed impossible to identify the molecules, and to find molecules with useful properties. Strategies of purification, identification, and screening were developed, however, to solve the problem. All these strategies are based on synthesis and testing of partial libraries.

The earliest strategy, the "Iteration method" is described in the above-mentioned document of Furka notarized in 1982. Identification of the sequence of the active peptide involves removal of samples after each coupling step of the synthesis before mixing. These samples are used in the step-by-step identification by testing and coupling starting at the N-terminus.

The "Positional scanning" method is based on synthesis and testing of a series of sub-libraries in which a certain sequence position in all components is occupied by the same amino acid.

"Omission libraries" in which a certain amino acid is missing from all peptides of the mixture as well as "amino acid tester libraries" that contain those peptides that are missing from the omission libraries can also be used in the deconvolution process.

If the peptides are not cleaved from the solid support we deal with a mixture of beads, each bead containing a single peptide. Smith and his colleagues showed earlier that peptides could be tested in tethered form, too. This approach was also used in screening peptide libraries. The tethered peptide library was tested with a dissolved target protein. The beads to which the protein was attached were picked out, removed the protein from the bead then the tethered peptide was identified by sequencing.

A somewhat different approach was followed by Taylor and Morken. They used infrared thermography to identify catalysts in non-peptide tethered libraries. When the beads were immersed into a solution of a substrate. the catalyst containing beads were glowing because of the heat evolved in them and could be picked out.

The components of combinatorial libraries can also be tested one by one after cleaving them from the individual beads.

If we deal with a non-peptide organic libraries library it is not as simple to determine the identity of the content of a bead as in the case of a peptide one. In order to circumvent this difficulty methods were developed to attach to the beads, in parallel with the synthesis of the library, molecules that encode the identity of the compound formed in the bead. The attached molecules may form peptide or nucleotide sequences or a binary code.

Chemical Informatics is Insight medical publisher journal and also one of the most emerging fields in the present scenario. It is a multidisciplinary field which covers the research containing molecular design tools for finding the best fitting compounds which address to particular targets.

Chemical Informatics is a vast field that aims to disseminate information regarding the design, structures, creation, dissemination, visualization and the use of chemical information. Chemical Informatics Journal aims to supply scientists of resources in order to provide the scientific knowledge through the publication of peer-reviewed, high quality, scientific papers and other material on all topics related to Chemical information, Software and databases.

Submission

Article submissions should be done using the online Editor Tracking System or through E-mail IDs provided at the respective journal’s site.

Submit manuscript to http://www.imedpub.com/submissions/chemical-informatics.html or as an E-mail attachment to our editorial office at chemicalinformatics@chemistryjournals.org

 

Contact

Elsa
Journal Manager

Whatsup: +44-20-3608-4181
Chemical Informatics-Open Acces