Nanogen Recognomics Gmbh

Sanofi-aventis

Thomas J Onofrey

Norbert Windhab

Markus Schweitzer

Charles Greef

Daguang Wang

John R Havens

Christoph Brücher

Stefan Raddatz

Jochen Müller-Ibeler

Compounds relating to attachment chemistries for binding biomolecules to a substrate surface are described. These include compounds of the following structure: The biomolecule includes a single nucleic acid, oligonucleotides, polynucleotides, DNAs, RNAs, proteins, peptides, enzymes, antibodies, CNAs (cyclohexyl nucleic acids), p-MeNAs (methyl or methoxy phosphate nucleic acids), peptide nucleic acids (PNAs), and pyranosyl RNAs (p-RNAs).

Biomolecules having multiple attachment moieties for binding to a substrate surface

Methods of binding biomolecules to a substrate are provided that include contacting the biomolecule with a branched linking moiety to form a branched linking structure. The branched linking structure is then contacted with a binding moiety on the substrate to form a coupled substrate binding structure, thereby binding the biomolecule to the substrate. The biomolecule may contain a Lewis base or a nucleophile to react with a Lewis acid or electrophile in the branched linking moiety. Alternatively, the biomolecule may contain a Lewis acid or electrophile that can react with a Lewis base or nucleophile in the branched linking moiety. Additionally, the biomolecule can be bound to the substrate through a covalent or non-covalent bond.

Biomolecules are provided having multiple binding sites for attachment to a substrate surface. The multiple attachment sites may be produced directly on the biomolecule or through use of branched phosphoramidite moieties that can be added in multiple to form dendritic structures which can in turn provide attachment sites for substrate binding moieties. Substrate binding moieties may include noncovalent binding moieties. For covalent binding moieties oligonucleotides containing hydrazides are provided. These hydrazides can be introduced via protected building blocks such as phosphoramidites or via building blocks containing precursor forms of such hydrazides.

This invention relates to attachment chemistries for binding macromolecules to a substrate surface or to other conjugation targets. More particularly, this invention relates to attachment chemistries involving branched or linear structures having one or more hydrazide attachment moieties for binding the macromolecules to a substrate surface, or for other conjugation reactions. Novel modifying reagents are provided for the introduction of protected hydrazide attachment moieties or precursor forms of such hydrazides to the macromolecule, either as a single hydrazide or as multiple hydrazides.

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Poway, CA, United States of America

Thomas J Onofrey