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Automated solid‐phase synthesis of linear nitrogen‐linked compounds
Author(s) -
Davis Peter W.,
Swayze Eric E.
Publication year - 2000
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(200024)71:1<19::aid-bit4>3.0.co;2-g
Subject(s) - combinatorial chemistry , amine gas treating , chemistry , bifunctional , monomer , amino acid , solid phase synthesis , scaffold , drug discovery , alkylation , organic chemistry , polymer , peptide , biochemistry , computer science , database , catalysis
A synthetic library motif has been developed to create linear, nitrogen‐linked compounds as screening libraries to target structured RNA for drug discovery. Scaffolds were created in situ from suitably protected bifunctional compounds linked together either by acyl or amine links. Acyl links were created from amino acids, which also introduce one degree of functionality. Amine links from the amino acid nitrogen were created from an N ‐protected amino alcohol via Fukuyama Mitsunobu alkylation. Each amine site can then be used for introducing functionality or extending the scaffold. This synthetic scheme can be used to create a wide variety of modified‐backbone PNA in situ, as shown by the synthesis of a PNA‐type monomer. The synthesis steps have been enabled on a 96‐well parallel‐array synthesizer for high‐throughput synthesis. The present study represents a versatile synthetic approach to a wide variety of potential RNA‐binding molecules. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng (Comb Chem) 71:19–27, 2000.