By Lisa B. English
BD Biosciences, San Jose, CA. Discusses numerous suggestions for combinatorial library synthesis and qc, screening, purification, and levels of computational ways. gains comprise combinatorial receptors, constitution verification, and synthesis of DNA-binding polyamides. Halftone illustrations incorporated.
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Extra resources for Combinatorial Library Methods and Protocols
This facilitates cleavage by TFA and provides a route to nitrogen-containing heterocyclic compounds (21,23,34). 2. Linkers Cleaved by Gaseous Reagents Liquid TFA and HF are typical cleavage reagents for acid-cleavable linkers. Alternatively, cleavage may be effected by the use of gaseous HCl or HF. The efficiency of gaseous HCl cleavage can be compared to diluted TFA; the effectiveness of gaseous HF is comparable to liquid HF. Among the commonly used acid-cleavable linkers, the esters of Merrifield resin 8 and carboxamides of the MBHA linker 9 (Fig.
It has been used to immobilize acids (1c), alcohols (3c), thiols, and amines (4c). The ease of linker cleavage can be further fine-tuned by substitutions on the aromatic ring (8,9). An electron-donating alkoxy group, as in linker 5, increases acid lability and is used in Wang (5a) (10) and Sheppard (29) linkers. Additional methoxy groups further increase acid lability, as documented for Sasrin (5b) (30) or PAL (5c) (31) linkers. The linker 6b having X = OMe and Y = H, referred to as AMEBA (acid-sensitive methoxybenzaldehyde) and linker 6c (32), X = Y = OMe, referred to as BAL (backbone amide linker) 6c (33) allow target compounds to be cleaved by TFA.
And Still, W. C. (1994) A general method for molecular tagging of encoded combinatorial chemistry libraries. J. Org. Chem. 59, 4723–4724. 32. Burbaum, J. , Ohlmeyer, M. H. , Reader, J. , Dillard, L. , Randle, T. , Sigal, N. , and Baldwin, J. J. (1995) A paradigm for drug discovery employing encoded combinatorial libraries. Proc. Natl. Acad. Sci. USA 92, 6027–6031. 33. , Holmes, C. , Murphy, M. , Jacobs, J. , Gordon, E. , and Gallop, M. A. (1996) Versatile approach to encoding combinatorial organic syntheses using chemically robust secondary amine tags.