Abstract: Methods of identifying molecular interaction sites in eukaryotic and prokaryotic nucleic acids, especially RNA, are described. Secondary structural elements are identified from highly conserved sequences. Methods of preparing databases relating to such molecular interaction sites are also provided herein as are databases themselves. Therapeutic, agricultural, industrial, and other applicability results from interaction of such molecular interaction sites with “small” and other molecules.
Type:
Grant
Filed:
May 12, 1998
Date of Patent:
April 24, 2001
Assignee:
ISIS Pharmceuticals, Inc.
Inventors:
David J. Ecker, Ranga Sampath, Richard Griffey, John McNeil
Abstract: 2'-O-alkylated guanosine, uridine, cytidine, and 2,6-diaminopurine 3'-O-phosphoramidites are prepared by alkylating nucleoside precursors, adding suitable blocking groups and phosphitylating. Alkylation is effected on 2,6-diamino-9-(.beta.-D-ribofuranosyl)purine followed by deamination to prepare guanosine 2'-O-alkylated 3'-O-phosphormidites. Alkylation is effected on a dialkyl stannylene derivative of uridine to prepare uridine 2'-O-alkylated 3'-O-phosphormidites. Alkylation is effected directly on cytidine to prepare cytidine 2'-O-alkylated 3'-O-phosphormidites. Alkylation is effected directly on 2,6-diaminopurine to prepare 2,6-diaminopurine 2'-O-alkylated 3'-O-phosphormidites.