Isis Pharmaceuticals, Inc.

Normand Hebert

Oscar L Acevedo

David J Ecker

Peter W Davis

Phillip Dan Cook

John S Kiely

Jacqueline R Wyatt

Muthiah Manoharan

Balkrishen Bhat

Clarence Frank Bennett

Neil Stowe

Oligomeric compounds comprising a plurality of aminodiol monomer subunits joined by linking groups are provided, as well as libraries of such compounds and processes for preparing the oligomeric compounds and libraries.

Oligomeric aminodiol-containing compounds, libraries thereof, and process of preparing the same

Chemical reaction apparatus, materials and methods are provided for the automatable, efficient synthesis of chemical species and libraries. In accordance with preferred embodiments, chemical droplet generation and direction techniques are employed to prepare oligomers and libraries of chemical species. Reaction assemblies adapted for efficient synthetic employment and for improved collection are also disclosed.

Chemical reaction apparatus and methods

Chemical synthesis apparatus employing a droplet generator

The present invention provides improved methods for tracking the biodistribution of macromolecules and carriers in cells. In accordance with one embodiment, oligonucleotides and lipid carriers are differentially fluorescently labeled and coadministered to the cells. Useful compounds and synthetic methods are also provided.

Methods and compounds for tracking the biodistribution of macromolecule-carrier combinations

Combinatorial libraries are constructed to include aminodiol monomer subunits connected by phosphodiester, phosphorothioate, or phosphoramidate linking moieties. Combinatorial libraries of the invention feature a plurality of functional groups attached to backbone and phosphoramidate combinatorial sites.

Combinatorial libraries having aminodiol monomer subunits

Chemical reaction apparatus for performing multiple reaction on a

Phosphate linked oligomers

Phosphoramidate and phosphorothiomidate oligomeric compounds

Pyrrolidine-containing monomers and oligomers

Compounds are provided having the structure: ##STR1## wherein the L groups are spanner or linker units, the Y and T group are functional groups for interacting with target molecules of interest, the X groups are oxygen or sulfur and the E groups are H, conjugate groups or intermediate groups used during the synthesis of the compounds are prepared using H phosphonate type chemistry wherein the functional groups are added during an oxidization step.

Phosphoramidate and phosphorothioamidate oligomeric compounds

Novel pyrrolidine monomers bearing various functional groups are used to prepare oligomeric structures. The pyrrolidine monomers can be joined via standard phosphate linkages including phosphodiester and phosphorothioate linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen-bonding.

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Cardiff, CA, United States of America

Normand Hebert