Glaxosmithkline LLC

Praecis Pharmaceuticals, Inc.

X-chem, Inc.

Paolo A Centrella

Richard W Wagner

Matthew Clark

Malcolm L Gefter

Barry A Morgan

Dennis R Benjamin

Christopher C Arico-Muendel

David I Israel

Malcolm J Kavarana

Stephen Paul Hale

Nils Jakob Vest Hansen

Raksha A Acharya

George J Franklin

Steffen Phillip Creaser

Steffan Phillip Creaser

Nils Jakob Hansen

Anthony Dominic Keefe

Ying Victor Zhang

Alexander Litovchick

John William Cuozzo

John W Cuozzo

Christopher D Hupp

Ying Zhang

Anthony D Keefe

Mathew A Clark

The present invention relates to oligonucleotide-encoded libraries and methods of tagging such libraries. In particular, the methods and oligonucleotides can include one or more 2'-substituted nucleotides, such as 2&#x2032;-O-methyl or 2&#x2032;-fluoro nucleotides, and other conditions or reagents to enhance enzyme ligation or one or more chemical functionalities to support chemical ligation.

Methods for tagging DNA-encoded libraries

The present invention provides a method of synthesizing libraries of molecules which include an encoding oligonucleotide tag.

Methods for synthesis of encoded libraries

The present invention provides a method for identifying a compound of interest by screening libraries of molecules which include an encoding oligonucleotide tag.

Methods for identifying compounds of interest using encoded libraries

The present invention provides methods of synthesizing a molecule comprising a functional moiety which is operatively linked to an encoding oligonucleotide. The methods include providing an initiator compound comprising an initial functional moiety comprising n building blocks, wherein the initial functional moiety comprises at least one reactive group, and is operatively linked to an initial oligonucleotide; reacting the initiator compound with a building block comprising at least one complementary reactive group, under conditions suitable for reaction of the complementary reactive group to form a covalent bond; and reacting the initial oligonucleotide with an incoming oligonucleotide corresponding to the building block in the presence of an enzyme which catalyzes ligation of the initial oligonucleotide and the incoming oligonucleotide, under conditions suitable for ligation of the incoming oligonucleotide and the initial oligonucleotide to form an encoding oligonucleotide.

The present invention provides methods of synthesizing libraries of molecules comprising a functional moiety which is operatively linked to an encoding oligonucleotide. The methods generally include providing a solution comprising initiator compounds comprising an initial functional moiety which comprises n building blocks which comprise at least one reactive group, which is operatively linked to an initial oligonucleotide; dividing the solution into reaction vessels; reacting the initiator compounds in each reaction vessel with a building block comprising a complementary reactive group to form a covalent bond; and reacting the initial oligonucleotide in each aliquot with a distinct incoming oligonucleotide in the presence of an enzyme which catalyzes the ligation of the incoming oligonucleotide and the initial oligonucleotide, under conditions suitable for enzymatic ligation of the incoming oligonucleotide and the initial oligonucleotide to form an encoding oligonucleotide which identifies the structure of the functional moiety.

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Acton, MA, United States of America

Paolo A Centrella