PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9873716

Mixed-backbone oligonucleotides as second-generation antisense agents with reduced phosphorothioate-related side effects.

W Zhou·S Agrawal
View original source ↗Export metadata ↓

Abstract

Mixed-backbone oligonucleotides containing alternative phosphorothioate and phosphodiester linkages in the 2'-O-methylribonucleosides segment show increased affinity with complementary targets, increased stability towards nucleases in vitro and in vivo, and reduced phosphorothioate-related prolongation of partial thromboplastin time compared to phosphorothioate oligodeoxynucleotides, thereby providing antisense agents with reduced side effects.

Explore related subjects

Drug StabilityHumansOligonucleotides, AntisensePartial Thromboplastin TimeStructure-Activity RelationshipThionucleotidesJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

W Zhou, S Agrawal. 1998-11-17. Mixed-backbone oligonucleotides as second-generation antisense agents with reduced phosphorothioate-related side effects.. https://doi.org/10.1016/s0960-894x(98)00591-5

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Pooling batches in drug stability study by using constant-width simultaneous confidence bands.

One important study objective in drug stability studies is to estimate the shelf-life of a drug. A key statistical problem involved in this is how to assess the practical equivalence of different batches of the same drug so that different batches can be subgrouped to produce a single shelf-life for the drug. In this paper constant-width simultaneous confidence bands are proposed to quantify the magnitude of difference between different batches, with a particular view to establish the practical equivalence of different batches. This approach is suitable for the situation that the intercepts and slopes of the regression lines for the batches cannot be assumed to be equal. It is shown how constant-width simultaneous confidence bands can be easily constructed for the multiple comparison of several general linear regression models. In particular, it is shown that constant-width simultaneous confidence bands have a better chance to establish the equivalence than, and so are preferable to, the hyperbola-shaped simultaneous confidence bands considered.

Drug Stability↗
PubMed2007

Model studies on the influence of matrix type and storage environment on the stability of a model aroma mixture during storage.

The objective of this study was to investigate the effect of oxygen in the storage atmosphere on the degradation of model compounds when present in water or a medium chain triglyceride (MCT) matrix. A model aroma compound mixture was prepared in oil (MCT) or water, and it was then stored under either an ambient air or argon atmosphere containing respectively ca. 20% and <0.5% residual oxygen. Samples were analyzed by SPME-GC/MS to determine the relative stability over time of different classes of aroma compounds. The low-oxygen atmosphere appeared to have a significant protective effect on sulfur compounds, aldehydes, and ketones in oil but a detrimental influence on pyrroles. Data showed little influence of the atmosphere for these compounds in water. In addition, the type of matrix had a significant effect (P < 0.05) on the stability of aldehydic, ester, and pyrrole compounds. These compounds were more stable in MCT than in water.

Drug Stability↗
PubMed2007

Kojic acid-tripeptide amide as a new tyrosinase inhibitor.

Twenty two kojic acid-tripeptide amides were prepared using a solid-phase Fmoc/tBu strategy with Rink Amide SURE(R) resin. To effectively obtain kojic acid-tripeptide amide conjugates, the coupling conditions of kojic acid to the tripeptide on the resin were optimized. The tyrosinase inhibitory activity of kojic acid-tripeptide amides and the effect of the amino acid sequence on the activity were compared with those of kojic acid-tripeptide acids. The stability of kojic acid-tripeptide amides were then compared with those of kojic acid and kojic acid-tripeptides acids. As a consequence, kojic acid-FWY-NH(2) proved to be the best compound, with the highest inhibitory activity, which was maintained over different storage times under various temperatures and pHs.

Drug Stability↗