Screening Combinatorial Libraries

It is important to note that the same ALIS hardware and software used for combinatorial library screening is applicable to characterizing protein-ligand interactions using the methods described below. 

S Roychoudhury, SE Blondelle, SM Collins, MC Davis, HD McKeever, RA Houghten, CN Parker. Use of combinatorial library screening to identify inhibitors of a bacterial two-component kinase. Molecular Diversity 4 173-182, 1998. 

A very powerful method for screening active peptides without knowing the actual sequence is the combinatorial peptide library. This method was first described by Houghten and coworkers for peptides synthesized on a polymer resin (53). Using combinatorial libraries, screening begins in theory... 

Cheng CC, Chu YH, Affinity capillary electrophoresis-mass spectrometry in combinatorial library screening, Am. Lab., 30 79-81, 1998. 

Peptidomimetic ligands for opioid receptors have also been identified from combinatorial libraries. Screening of an N-(substi-tuted)glycine peptoid library for affinity for ix opioid receptors yielded novel structures (251) with high affinity for these receptors (K = 6-46 nM) (953). A library of dipeptide amides with alkyl substituents on both the interior and C-terminal amides were prepared, and high affinity agonists for all three opioid receptors identified from the library (see Ref 946). Peptide libraries can also be further modified ["libraries from libraries" (954)] to yield new potential ligands for receptors. Thus an acety-... 

Figure 12 PUF-MS as used in combinatorial library screening is used to separate macromolecular bound library components from unbound ones. Mass spectrometry is used to identify the bound components after they have been released from the receptor.

Mass spectrometry and isotope techniques can be used effectively for the encoding/decoding of pooled libraries. Two of these techniques are mass encoding [44] and stable isotope encoding [44,45]. Because stable isotope encoding is more direct and lends itself more readily to combinatorial library screening with mass spectrometry, it is discussed below. 

Goldman, E. R. Youvan, D. C. (1992) An algorithmically optimized combinatorial library screened by digital imaging spectroscopy. Bio/Tcc/mo/ogy 10, 1557-1561. 

Due to a size dependence of light scattering two-color or multicolor scattering is feasible. This technique allows to discriminate in between multiple interaction family e.g. in combinatorial library screening. 

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