Glaxosmithkline LLC

Paulo A Centrella

Malcolm L Gefter

Barry A Morgan

Richard W Wagner

Dennis R Benjamin

Christopher C Arico-Muendel

David I Israel

Malcolm J Kavarana

Matthew Clark

Stephen Paul Hale

Nils Jakob Vest Hansen

Raksha A Acharya

George J Franklin

Steffen Phillip Creaser

The present invention provides methods of synthesizing libraries of molecules comprising a functional moiety which is operatively linked to an encoding oligonucleotide, wherein the encoding oligonucleotide comprises a capping sequence containing degenerate nucleotides. The methods generally include providing a solution comprising initiator compounds comprising an initial functional moiety comprising n building blocks 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.

Methods for synthesis of encoded libraries

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Acton, MA, United States of America

Paulo A Centrella