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A combinatorial synthesis of tyrphostins via the “directed sorting” method
Author(s) -
Shi Shuhao,
Xiao Xiaoyi,
Czarnik Anthony W.
Publication year - 1998
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/(sici)1097-0290(199824)61:1<7::aid-bit4>3.0.co;2-n
Subject(s) - combinatorial chemistry , sorting , mass spectrometry , characterization (materials science) , chemistry , solid phase synthesis , phase (matter) , organic synthesis , computer science , chromatography , materials science , nanotechnology , organic chemistry , catalysis , biochemistry , algorithm , peptide
Abstract Using solid‐phase organic synthesis, we have prepared a 432‐member (18 × 8 × 3) sample library based on the AG 490 “tyrphostin” template. By utilizing 432 reactors each equipped with a unique radiofrequency memory ID tag, the 432 products could be obtained as discrete entities (i.e., not as mixtures) via 18 + 8 + 3, or 29 reactions. Reading each ID tag after each reaction step permitted the “directed sorting” of reactors into appropriate reaction vessels containing multiple reactors. After synthesis, all products were cleaved from the solid‐phase support and lyophilized to afford powders. Characterization of 5% of the library members by NMR and mass spectrometry provided verification of structure. In addition, TLC analysis of every library member provided evidence that most (or all) are composed of a single major organic compound. Some 88% of these samples were obtained in amounts of between 5 and 19 mg. Using this reaction sequence and the “directed sorting” approach, the synthesis of much larger AG 490‐based libraries can be envisioned. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng (Comb Chem) 61:7–12, 1998.