Oligonucleotide library

Ho SP, Britton DH, Stone BA, et al. Potent antisense oligonucleotides to the human multidrug resistance-1 mRNA are rationally selected by mapping RNA-accessible sites with oligonucleotide libraries. Nucleic Acids Res 1996 24 1901-1907. 

Oligonucleotide library/RNase H digestion-based screening... 

Famulok, M. and Jenne, A. (1998) Oligonucleotide libraries-variatio delectat. Curr. Opin. Chem. Biol., 2, 320-327. Famulok, M. and Mayer, G. (1999) Aptamers as tools in molecular biology and immunology. Curr. Top. Microbiol. Immunol., 243, 123-136. 

The essential step during in-vitro selection is amplification of the rare species represented in the combinatorial oligonucleotide library that bind to the target molecule. Amplification of nucleic acids can be accomplished very easily by employing enzymes - DNA polymerases (Box 16) - in a process called PCR. On the other hand, the degradation of aptamers occurs as a result of abundant nucleases which attack specific sites within the naturally configured nucleic acids. 

Automated synthesis of peptide and oligonucleotide libraries was initiated about 10 years ago [4], Within the last three years, there has been much attention focused on the generation of combinatorial libraries of small molecules. As with biopolymers, the use of solid resin support was central to the advance of this field. In solid-phase synthesis, one of the reactants is covalently bound to the solid support and an excess of the other reactants may be used in each step to drive reactions to completion. Purification of the intermediates and final product is easily achieved through extensive washing of the resin after each chemical step. For the purpose of high throughput synthesis, cleavage of the final... 

With peptide and oligonucleotide libraries prepared by split synthesis, the structure of a bound ligand on an individual bead can be determined by microsequencing [ 17,18]. This approach has been applied to testing libraries where the bead bound compounds are evaluated for their ability to bind to monoclonal antibodies or other recognition macromolecules. In one such approach, fluorescence-based methods are used to select the most... 

This is, together with positional scanning, the most popular deconvolution technique. It was introduced by Geysen et al. [9] and exploited by Houghten et al. [10] and Ecker et al. [11] for the deconvolution of peptide and oligonucleotide libraries, but it has been applied to the deconvolution of many small molecule libraries. 

This method was presented by Freier et al. [44] and was intended as a refinement of other existing deconvolution techniques. While the only reported example deals with virtual oligonucleotide libraries, the technique looks promising and useful also for real small organic molecule libraries. 

The choice of an oligonucleotide library came from the notion that oligonucleotide hybridization can be calculated accurately, even for large... 

Topics include the generation of molecular diversity by chemical methods using solution- and solid-phase chemistries, biological approaches for the production and screening of peptides, antibody and oligonucleotide libraries, and the application of computer-assisted approaches to guide library synthesis. 

Oligonucleotide libraries are commonly used either to encode biosynthetic display peptide libraries (Section 11.1) or to screen for novel nucleotide ligands (aptamer) or catalytic activities (ribozymes). They are produced using high-quality automated ON SP protocols seen in Section 2.2, but their amplification and selection are performed via biological protocols (see Sections 4.2.4 and 11.2). 

Unrandomization of Random Oligomer Fragments) (173) have been applied either on SP or in solution to peptide or oligonucleotide library deconvolution, but none have found relevant applications in small organic molecule libraries. Several reviews dealing with deconvolution methods for SP libraries were mentioned in the previous... 

BIOSYNTHETIC OLIGONUCLEOTIDE LIBRARIES 531 10.2.2 In Vitro Selection of ON Sequences... 

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