Abstract: Oligonucleotide analogs are provided having improved nuclease resistance. Modifications of selected nucleotides through substitutions on the pyrimidine ring are disclosed. Certain preferred embodiments comprise the inclusion of said modified nucleotides at a plurality of sites, especially at the 3' end of a selected oligonucleotide analog.

Abstract: Compounds of formula I; ##STR1## wherein R.sup.1 is hydrogen, or a blocking group that is compatible with oligonucleotide synthesis;R.sup.2 is hydrogen, nitro, lower alkyl amino, diloweralkyl amino or methyl;R.sup.3 is hydrogen or --P(R.sup.4)OR.sup.5 ;R.sup.4 is chlorine, 4-nitroimidazole, imidazole, tetrazole, triazole or di(lower-alkyl)amino-;R.sup.5 is methyl, 2-cyanoethyl or 2,2,2-trichloroethyl;n is from 0 to 2X is oxygen, sulfur, or --NR.sup.6 ;R.sup.6 is hydrogen or lower alkyl;Q is chosen from the group consisting of ##STR2## R.sup.7 is lower-alkyl or loweralkyloxy methylene; and R.sup.8 is hydrogen, benzoyl, anisoyl, or lower-alkyl carbonyland its pharmaceutically acceptable addition salts are nucleotide analogs. Modified oligonucleotides containing the nucleoside analogs of formula I are stable to nuclease degradation and are useful in inhibiting gene expression, in sequencing, and in mutagenesis.

Abstract: Therapeutic oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in wild type oligomers with four atom linking groups forms unique di- and poly- nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

Abstract: Novel oligonucleotide analogs are provided having improved cellular uptake, improved resistance to nucleases, and good hybridization to target RNA. Such analogs are provided having substantially non-chiral, non-ionic linking functionalities between the sugars and sugar analogs thereof. In accordance with preferred embodiments, the 4' position of a sugar or sugar analog at one nucleoside is linked to the 3' position of a second sugar or sugar analog of a second nucleoside by a linking function that comprises a two- or three- carbon backbone chain. In accordance with preferred embodiments, the linking functions comprise the formula)--R.sub.1 --O where R.sub.1 comprises a two or three carbon backbone. Such linking functions also, preferably comprise ether functionalities to effect such linkage. Processes for the automated synthesis of oligonucleotide analogs are also provided.

Abstract: Oligonucleotide analogs are provided having improved cellular uptake and improved nuclease resistance. Modification of oligonucleotides through the attachment of nitrogenous moieties, especially polyamines, hydrazines and the like to nucleosidic portions of the analogs is disclosed. Oligonucleotides targeted at the tat region of HIV comprise certain preferred embodiments.

Abstract: Oligonucleotide analogs are provided having improved cellular uptake and improved nuclease resistance. Modification of oligonucleotides through the attachment of nitrogenous moieties, especially polyamines, hydrazines and the like to nucleosidic portions of the analogs is disclosed. Oligonucleotides targeted at the tat region of HIV comprise certain preferred embodiments.