Encoded Synthetic Libraries

Felder ER, Heizmann G, Matthews IT, Rink H, Spieser E, A new combination of protecting groups and links for encoded synthetic libraries suited for consecutive tests on the solid phase and in solution, Mol. Diversity, 1 109-112, 1995. 

Products/technologies ESL (Encoded Synthetic Library) technology enables the identification of individual organic compounds from combinatorial librar-... 

DG Jones. Applications of encoded synthetic libraries in ligand discovery. Polymer Prep. 35 981-982, 1994. 

Still, W. C. Discovery of sequence-selective peptide binding by synthetic receptors using encoded combinatorial libraries. Acc. Chem. Res. 1996,29,155-163. 

The concept of tweezer-like two-armed molecules was used to construct synthetic receptor molecules based on methylene sulfonamide peptidomimetics.11291 When screened for binding against an encoded tripeptide library, one of the synthetic receptors demonstrated a remarkable binding selectivity 11291 the synthetic receptor affinity could be further increased by varying the hinge part of the peptidomimetic molecule.11301... 

In ribosome display, the physical link between genotype and phenotype is accomplished by mRNA-ribosome—protein complexes, which are directly used for selection. If a library of different mRNA molecules is translated, a protein library results in which each protein is produced from its own mRNA and remains connected to it. Since these complexes of the proteins and their encoding mRNAs are stable for several days under the appropriate conditions, very stringent selections can be performed. As all steps of ribosome display are carried out in vitro, reaction conditions of the individual steps can be tailored to the requirements of the protein species investigated, as well as the objectives of the selection or evolution experiment. Application of ribosome display has produced scFv fragments of antibodies with affinities in the picomolar range from libraries prepared from immunized mice (Hanes et al., 1998) and more recently from a naive, completely synthetic library (Hanes et al., 2000), and has been used to evolve improved off-rates and stability (Jermutus et al., 2000). 

Needels MC, Jones DG, Tate EH, Heinkel GL, Kochersperger LM, Dower WJ, Barrett RW, Gallop MA, Generation and screening of an oligonucleotide-encoded synthetic peptide library, Proc. Natl. Acad. Sci. USA, 90 10700-10704, 1993. 

The selected example by Maclean et al. [40] reported a 240-member encoded pyrrolidine library, whose synthetic scheme is reported in Figure 9.12. Coupling of the resin bound acid labile linker FIMPB (4-hydroxymethyl-3-methoxyphenoxybutyric acid) with the first monomer set (four Fmoc amino acids, A) was followed by its coding (tags Ti-T3), and by coding of the second monomer set B (tags T4-T6) then the second monomer set (four aldehydes, B) was added and the reactive imines were immediately reacted with the third... 

Baldwin JJ, Design, synthesis and use of binary encoded synthetic chemical libraries, Molecular Diversity, 2 81-88, 1996. 

Burger MT, Still WC, Synthetic ionophores. Encoded combinatorial libraries of cyclen-based receptors for Cu(2+) and Co(2+), J. Org. Chem., 60 7382-7383, 1995. 

Francis et al. (227) reported the synthesis of a > 10,000-member encoded SP pool library L37 characterized by a turn element (monomers M2, prepared using simple synthetic routes) surrounded by two a-amino acids (monomers Mi and M3) and capped on the N-terminus (monomers M4). The structure of the library and the monomer sets are reported in Fig. 9.52. Mix-and-split protocols and a popular encoding method (177) were used to prepare and encode the library. 

A Borchardt, WC Still. Synthetic receptor binding elucidated with an encoded combinatorial library. J Am Chem Soc 116 373-374, 1994. 

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