"Libraries from libraries": chemical transformation of combinatorial libraries to extend the range and repertoire of chemical diversity.

Abstract

The generation of diverse chemical libraries using a "libraries from rie" concept is described. The MATERIALS AND METHODSThe benzyl protecting group was used for the side-chain protection of asparagine, glutamate, serine, and threonine; methoxybenzyl for cysteine; dinitrophenyl for histidine; chlorobenzyloxycarbonyl for lysine; sulfoxide for methionine; tosyl for arginine; formyl for tryptophan; and bromobenzyloxycarbonyl for tyrosine. Other reagents and materials used have been described (13).Permethylation of Protected Peptides. Twenty model peptide resins (110 mg, 0.1 milliequivalent each) with defined sequences (represented as OGGFL-resin, "0" individually representing each of the 20 naturally occurring amino acids) were prepared on methylbenzhydrylamine resin (mBHA) (0.90 milliequivalent per g) using t-butoxycarbonyl (Boc) chemistry combined with simultaneous multiple peptidesynthesis techniques as described (13). After removal of the final N-a-Boc protecting group, each of the side-chainprotected resins were then permethylated as described below. The resin-bound PS-SPCL was prepared as described (2,12).In a typical example, AGGFL-mBHA resin (90 mg, 0.1 milliequivalent), contained within an individual polypropylene mesh packet (13) 11138The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Selective Agonists and Antagonists of Formylpeptide Receptors: Duplex Flow Cytometry and Mixture-Based Positional Scanning Libraries

“…Using solid-phase chemistry approaches, mixturebased libraries were synthesized from resin-bound amino acids, peptides, and peptidomimetics as starting materials using the simultaneous multiple synthesis and "libraries from libraries" approaches, as previously described (Houghten, 1985;Houghten et al, 1991Houghten et al, , 1999Ostresh et al, 1994a;Nefzi et al, 2004). Extensive optimization of each reaction condition was necessary for mixture library generation.…”

“…The synthesis of library 1344 (including 1343, 1345, 1346, and 1347) has been previously described (Reilley et al, 2010). In brief, library 1344 was synthesized using the "libraries from libraries" approach (Ostresh et al, 1994a;Nefzi et al, 2004) starting with resin-bound N-acylated peptides (Hensler et al, 2006), which were subsequently exhaustively reduced with boranetetrahydrofuran. No loss of chirality was found in either the reduction or subsequent steps.…”

Identification of Novel Bioactive Hexapeptides Against Phytopathogenic Bacteria Through Rapid Screening of a Synthetic Combinatorial Library

“…These results suggest that using D-enantiomers may be a useful approach to improving AMP stability. An alternative approach is the use of peptidomimetics [28]. Expression of AMPs in transgenic plants could provide another means of conferring protection against pathogens [25].…”

Natural product-like combinatorial libraries

“…151 Based on the fact that many natural and designed benzopyrans that contain modifications of the pyran olefin exhibit higher and/or different activity than that of the parent molecule (ex. β-lapachone, (+)-kellactone) ( Figure 41), [162][163][164] the Nicolaou group 165 developed a solution-phase "library-from-library" strategy 166 in which the previous libraries were employed for further derivatization at the pyran olefin, thereby increasing the structural diversity.…”