IP Library › Granted Patent US 12,655,420
Granted Patent B2
US 12,655,420 · App. 17/511,467 · Granted Jun 16, 2026

Oligonucleotide directed and recorded combinitorial synthesis of encoded probe molecules

Inventor: Richard Edward Watts (San Carlos, CA)
Assignee: Insitro, Inc.
C12N15/1093C12Q1/68C12Q1/6811C12Q1/6813C40B10/00C12Q2525/161C12Q2525/301C12Q2565/514C40B30/04
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Quick Facts
Patent No.
US 12,655,420
App. No.
17/511,467
Granted
Jun 16, 2026
Kind
B2
Abstract

The present disclosure relates to multifunctional molecules, including molecules according to formula (I): ([(B 1 ) M -D-L 1 ] Y —H 1 ) O -G-(H 2 -[L 2 -E-(B 2 ) K ] W ) P ,  (I) wherein G, H 1 , H 2 , D, E, B 1 , B 2 , M, K, L 1 , L 2 , O, P, Y, and W are defined herein. The present disclosure also relates to methods of preparing and using such multifunctional molecules to identify encoded molecules capable of binding target molecules.

Claims (86)

1 . A probe molecule, wherein the probe molecule is according to formula (I),

([(B 1 ) M -D-L 1 ] Y —H 1 ) O -G-(H 2 -[L 2 -E-(B 2 ) K ] W ) P ,  (I)

wherein

G is an oligonucleotide, the oligonucleotide comprising at least two coding regions encoding positional building blocks and a first terminal coding region encoding a first building block and a second terminal coding region encoding a second building block, wherein the at least two coding regions are single stranded and the first and second terminal coding regions are single or double stranded;

H 1 is a hairpin structure comprising oligonucleotides comprising a loop portion, a stem portion, and a 5′ single stranded portion, wherein H 1 comprises a 5′ end that is complementary to an end of the oligonucleotide G;

H 2 is a hairpin structure comprising oligonucleotides comprising a loop portion, a stem portion, and a 3′ single stranded portion, wherein H 2 comprises a 3′ end that is complementary to an end of the oligonucleotide G;

D is the first building block;

E is the second building block, wherein D and E are the same or different;

B 1 is a positional building block and M represents an integer from 1 to 20;

B 2 is a positional building block and K represents an integer from 1 to 20, wherein B 1 and B 2 are the same or different, wherein M and K are the same or different;

L 1 is a linker that covalently bonds D to the loop portion or the stem portion of H 1 ;

L 2 is a linker that covalently bonds E to the loop portion or the stem portion of H 2 ;

O is 1;

P is 1;

Y is an integer from 1 to 5;

W is an integer from 1 to 5; and

wherein at least one of each positional building block B 1 at position M and B 2 at position K is identified by one of the coding regions, and wherein at least one of the first building block D and second building block E is identified by at least one of the first and second terminal coding regions.

2 . The probe molecule of claim 1 , wherein G comprises a sequence represented by the formula (C N —(Z N —C N+1 ) A ), wherein C is a coding region, Z is a non-coding region, N is an integer from 1 to 20, and A is an integer from 1 to 20;

wherein each non-coding region contains from 4 to 50 nucleotides and is optionally double stranded.

3 . The probe molecule of claim 1 , wherein at least one of Y and W is an integer from 1 to 2.

4 . The probe molecule of claim 1 , wherein each coding region contains from 6 to 50 nucleotides.

5 . The probe molecule of claim 1 , wherein at least one of H 1 and H 2 comprises from 20 to 90 nucleotides.

6 . The probe molecule of claim 1 , wherein each coding region contains from 12 to 40 nucleotides.

7 . The probe molecule of claim 1 , wherein Y is an integer from 1 to 2, and each coding region contains from 12 to 40 nucleotides.

8 . The probe molecule of claim 1 , wherein W is an integer from 1 to 2, and each coding region contains from 12 to 40 nucleotides.

9 . The probe molecule of claim 1 , wherein a plurality of positional building blocks at B 1 and B 2 are different.

10 . A method of identifying probe molecules capable of binding or selecting for a target molecule comprising:

exposing the target molecule to a pool of probe molecules, wherein the probe molecules are according to claim 1 ,

removing at least one probe molecule that does not bind the target molecule,

amplifying at least one oligonucleotide G from the at least one probe molecule that was not removed from the target molecule to form a copy sequence,

sequencing at least one oligonucleotide G of the copy sequence to identify the at least two coding regions of the probe molecule to further identify at least one of each positional building block B 1 at position M and B 2 at position K, and to identify the at least one terminal coding region of the copy molecule to further identify at least one of the first building block D and the second building block E of the probe molecule.

11 . A method of forming a probe molecule, wherein the probe molecule is according to formula (I), the method comprising:

providing at least one hybridization array, the at least one hybridization array comprising at least one single stranded anti-codon oligomer immobilized on the at least one hybridization array, wherein the at least one single stranded anti-codon oligomer immobilized on the at least one hybridization array is capable of hybridizing to a coding region of a molecule of formula (II):

([(B I ) (M−I) -D-L 1 ] Y —H I ) O -G-(H 2 -[L 2 -E-(B 2 ) (K−1) ] W ) P   (II)

wherein

G is an oligonucleotide, the oligonucleotide comprising at least two coding regions encoding positional building blocks and a first terminal coding region encoding a first building block and a second terminal coding region encoding a second building block, wherein the at least two coding regions are single stranded and the first and second terminal coding regions are single or double stranded;

H 1 is a hairpin structure comprising oligonucleotides comprising a loop portion, a stem portion, and a 5′ single stranded portion, wherein H 1 comprises a 5′ end that is complementary to an end of the oligonucleotide G;

H 2 is a hairpin structure comprising oligonucleotides comprising a loop portion, a stem portion, and a 3′ single stranded portion, wherein H 2 comprises a 3′ end that is complementary to an end of the oligonucleotide G;

D is the first building block;

E is the second building block, wherein D and E are the same or different;

B 1 is a positional building block and M represents an integer from 1 to 20;

B 2 is a positional building block and K represents an integer from 1 to 20, wherein B 1 and B 2 are the same or different, wherein M and K are the same or different;

L 1 is a linker that covalently bonds D to the loop portion or the stem portion of H 1 ;

L 2 is a linker that covalently bonds E to the loop portion or the stem portion of H 2 ;

O is 1;

P is 1;

Y is an integer from 1 to 5;

W is an integer from 1 to 5; and

wherein at least one of each positional building block B 1 at position M and B 2 at position K is identified by one of the coding regions and wherein at least one of the first building block D and second building block E is identified by at least one of the first and second terminal coding regions;

sorting a pool of molecules of formula (II) into sub-pools by hybridizing a coding region of a sub-pool of molecules of formula (II) to the at least one single stranded anti-codon oligomer immobilized on the at least one hybridization array;

a step of optionally releasing the sub-pool of molecules of formula (II) from the at least one hybridization array into separate containers;

providing at least one of positional building blocks B 1 and B 2 ; and

reacting the at least one of positional building blocks B 1 and B 2 with the molecule of formula (II) to form a sub-pool of probe molecules of formula (I):

([(B 1 ) M -D-L 1 ] Y —H 1 ) O -G-(H 2 -[L 2 -E-(B 2 ) K ] W ) P ,  (I)

wherein

G is an oligonucleotide, the oligonucleotide comprising at least two coding regions encoding positional building blocks and a first terminal coding region encoding a first building block and a second terminal coding region encoding a second building block, wherein the at least two coding regions are single stranded and the first and second terminal coding regions are single or double stranded;

H 1 is a hairpin structure comprising oligonucleotides comprising a loop portion, a stem portion, and a 5′ single stranded portion, wherein H 1 comprises a 5′ end that is complementary to an end of the oligonucleotide G;

H 2 is a hairpin structure comprising oligonucleotides comprising a loop portion, a stem portion, and a 3′ single stranded portion, wherein H 2 comprises a 3′ end that is complementary to an end of the oligonucleotide G;

D is the first building block;

E is the second building block, wherein D and E are the same or different;

B 1 is a positional building block and M represents an integer from 1 to 20;

B 2 is a positional building block and K represents an integer from 1 to 20, wherein B 1 and B 2 are the same or different, wherein M and K are the same or different;

L 1 is a linker that covalently bonds D to the loop portion or the stem portion of H 1 ;

L 2 is a linker that covalently bonds E to the loop portion or the stem portion of H 2 ;

O is 1;

P is 1;

Y is an integer from 1 to 5;

W is an integer from 1 to 5; and

wherein at least one of each positional building block B 1 at position M and B 2 at position K is identified by one of the coding regions, and wherein at least one of the first building block D and second building block E is identified by at least one of the first and second terminal coding regions.

12 . The method of claim 11 , wherein the molecule of formula (II) is prepared by:

providing an oligonucleotide G′, the oligonucleotide G′ comprising at least two coding regions and at least one terminal coding region, wherein the at least two coding regions are single stranded, the at least one terminal coding region is single stranded, and the at least one terminal coding region at a 5′ and/or a 3′ end of the oligonucleotides G′ is different;

providing at least one charged carrier anti-codon, the at least one charged carrier anti-codon having the formula of ([(B 1 ) (M−1) -D-L 1 ] Y -H 1 ) and/or (H 2 -[L 2 -E-(B 2 ) (K−1) ] W );

combining the oligonucleotide G′ and the at least one charged carrier anti-codon;

bonding the 5′ end of the oligonucleotide G′ to the 3′ end of H 1 , and/or bonding the 3′ end of the oligonucleotide G′ to the 5′ end of H 2 to form the pool of molecules of formula (II):

([(B I ) (M−I) -D-L 1 ] Y —H I ) O -G-(H 2 -[L 2 -E-(B 2 ) (K−1) ] W ) P   (II)

wherein G, H 1 , H 2 , D, E, B 1 , B 2 , L 1 , L 2 , O, P, Y, and W are as defined in claim 11 , and M and K are one.

13 . The method of claim 11 , further comprising:

removing an oligonucleotide portion from the at least one terminal coding region of a probe molecule of formula (I) or molecule of formula (II).

14 . The method of claim 11 , further comprising:

ligating at least one of H 1 to G and H 2 to G.

15 . The method of claim 11 , wherein G comprises a sequence represented by the formula (C N —(Z N —C N+1 ) A ), wherein C is a coding region, Z is a non-coding region, N is an integer from 1 to 20, and A is an integer from 1 to 20;

wherein each non-coding region contains from 4 to 50 nucleotides and is optionally double stranded.

16 . The method of claim 11 , wherein at least one of Y and W is an integer from 1 to 2.

17 . The method of claim 11 , wherein at least one of H 1 and H 2 comprises from 20 to 90 nucleotides.

18 . The method of claim 11 , wherein Y is an integer from 1 to 2, and each coding region contains from 12 to 40 nucleotides; and/or

W is an integer from 1 to 2, and each coding region contains from 12 to 40 nucleotides.

Assignments (3)
MERGER Recorded Apr 15, 2025
From: HAYSTACK SCIENCES CORPORATION
To: HOCKEY INTERMEDIATECO, INC.
Reel/Frame 070846/0136 →
MERGER Recorded Apr 15, 2025
From: HOCKEY INTERMEDIATECO, INC.
To: INSITRO, INC.
Reel/Frame 070846/0245 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 27, 2021
From: WATTS, RICHARD EDWARD
To: HAYSTACK SCIENCES CORPORATION
Reel/Frame 057938/0247 →
Continuity (3)
Continuation 16306356
Provisional Application 62351046 · Jun 16, 2016
Related Publication 20220154179A1 · May 19, 2022
References Cited (181)
US 5573905A · Lerner et al. · 1996 [cited by applicant]
US 5723598A · Lerner et al. · 1998 [cited by applicant]
US 5759779A · Dehlinger · 1998 [cited by applicant]
US 6060596A · Lemer et al. · 2000 [cited by applicant]
US 6440723B1 · Dale · 2002 [cited by applicant]
US 7070928B2 · Liu et al. · 2006 [cited by applicant]
US 7223545B2 · Liu et al. · 2007 [cited by applicant]
US 7413854B2 · Pedersen et al. · 2008 [cited by applicant]
US 7442160B2 · Liu et al. · 2008 [cited by applicant]
US 7479472B1 · Harbury et al. · 2009 [cited by applicant]
US 7491494B2 · Liu et al. · 2009 [cited by applicant]
US 7557068B2 · Liu et al. · 2009 [cited by applicant]
US 7622279B2 · Ju · 2009 [cited by applicant]
US 7704925B2 · Gouliaev et al. · 2010 [cited by applicant]
US 7727713B2 · Pedersen et al. · 2010 [cited by applicant]
US 7771935B2 · Liu et al. · 2010 [cited by applicant]
US 7795424B2 · Liu et al. · 2010 [cited by applicant]
US 7883869B2 · Liu et al. · 2011 [cited by applicant]
US 7915201B2 · Franch et al. · 2011 [cited by applicant]
US 7928211B2 · Hansen et al. · 2011 [cited by applicant]
US 7935658B2 · Morgan et al. · 2011 [cited by applicant]
US 7972992B2 · Morgan et al. · 2011 [cited by applicant]
US 7972994B2 · Morgan et al. · 2011 [cited by applicant]
US 7989395B2 · Morgan et al. · 2011 [cited by applicant]
US 7998904B2 · Liu et al. · 2011 [cited by applicant]
US 8017323B2 · Liu et al. · 2011 [cited by applicant]
US 8071739B2 · Milton et al. · 2011 [cited by applicant]
US 8114636B2 · Agnew et al. · 2012 [cited by applicant]
US 8168381B2 · Rasmussen · 2012 [cited by applicant]
US 8183178B2 · Liu et al. · 2012 [cited by applicant]
US 8193335B2 · Carell et al. · 2012 [cited by applicant]
US 8202823B2 · Hansen et al. · 2012 [cited by applicant]
US 8206901B2 · Freskgard et al. · 2012 [cited by applicant]
US 8206914B2 · Liu et al. · 2012 [cited by applicant]
US 8298792B2 · Ju et al. · 2012 [cited by applicant]
US 8410028B2 · Morgan et al. · 2013 [cited by applicant]
US 8541570B2 · Gee et al. · 2013 [cited by applicant]
US 8552173B2 · Skrzypczynski et al. · 2013 [cited by applicant]
US 8642514B2 · Neri et al. · 2014 [cited by applicant]
US 8673824B2 · Neri et al. · 2014 [cited by applicant]
US 8691729B2 · Liu et al. · 2014 [cited by applicant]
US 8808984B2 · Pedersen et al. · 2014 [cited by applicant]
US 8846883B2 · Brown et al. · 2014 [cited by applicant]
US 8932992B2 · Pedersen et al. · 2015 [cited by applicant]
US 8951728B2 · Rasmussen · 2015 [cited by applicant]
US 8951782B2 · Rasmussen · 2015 [cited by applicant]
US 9006150B2 · Hansen et al. · 2015 [cited by applicant]
US 9096951B2 · Freskgard et al. · 2015 [cited by applicant]
US 9109248B2 · Freskgard et al. · 2015 [cited by applicant]
US 9121110B2 · Gouliaev et al. · 2015 [cited by applicant]
US 9175340B2 · Liu et al. · 2015 [cited by applicant]
US 10011868B2 · Liu et al. · 2018 [cited by applicant]
US 10036013B2 · Kim · 2018 [cited by applicant]
US 10053725B2 · Liu et al. · 2018 [cited by applicant]
US 10240147B2 · Decurtins et al. · 2019 [cited by applicant]
US 10513700B2 · Hansen et al. · 2019 [cited by applicant]
US 10669538B2 · Pederson et al. · 2020 [cited by applicant]
US 11186836B2 · Watts · 2021 [cited by examiner]
US 20050032081A1 · Ju et al. · 2005 [cited by applicant]
US 20050247001A1 · Carell et al. · 2005 [cited by applicant]
US 20060121470A1 · Pedersen · 2006 [cited by applicant]
US 20060269920A1 · Freskgard et al. · 2006 [cited by applicant]
US 20070026397A1 · Freskgard et al. · 2007 [cited by applicant]
US 20070213519A1 · Gouliaev et al. · 2007 [cited by applicant]
US 20080305957A1 · Thisted et al. · 2008 [cited by applicant]
US 20090011957A1 · Gouliaev et al. · 2009 [cited by applicant]
US 20090143232A1 · Pedersen et al. · 2009 [cited by applicant]
US 20090239211A1 · Freskgard et al. · 2009 [cited by applicant]
US 20090240030A1 · Ju et al. · 2009 [cited by applicant]
US 20090264300A1 · Franch et al. · 2009 [cited by applicant]
US 20100261181A1 · Agnew et al. · 2010 [cited by applicant]
US 20110020799A1 · Ogi et al. · 2011 [cited by applicant]
US 20120053091A1 · Wagner · 2012 [cited by applicant]
US 20120071329A1 · Morgan et al. · 2012 [cited by applicant]
US 20120142060A1 · Makarov et al. · 2012 [cited by applicant]
US 20120245040A1 · Morgan et al. · 2012 [cited by applicant]
US 20120252010A1 · Balasubramanian et al. · 2012 [cited by applicant]
US 20130005581A1 · Hansen et al. · 2013 [cited by applicant]
US 20130040823A1 · Freskgard et al. · 2013 [cited by applicant]
US 20130046083A1 · Brown et al. · 2013 [cited by applicant]
US 20130231473A1 · Brown et al. · 2013 [cited by applicant]
US 20130237459A1 · Rasmussen · 2013 [cited by applicant]
US 20130280700A1 · Ju et al. · 2013 [cited by applicant]
US 20130281324A1 · Gouliaev et al. · 2013 [cited by applicant]
US 20140235509A1 · Rasmussen · 2014 [cited by applicant]
US 20140295414A1 · Salic et al. · 2014 [cited by applicant]
US 20140315762A1 · Keefe et al. · 2014 [cited by applicant]
US 20140336079A1 · Agnew et al. · 2014 [cited by applicant]
US 20150050697A1 · Kim · 2015 [cited by applicant]
US 20150051088A1 · Kim · 2015 [cited by applicant]
US 20150051116A1 · Kim · 2015 [cited by applicant]
US 20150126381A1 · Rasmussen · 2015 [cited by applicant]
US 20150203841A1 · Rasmussen · 2015 [cited by applicant]
US 20150211002A1 · Keefe et al. · 2015 [cited by applicant]
US 20150232957A1 · Fournier-Wirth et al. · 2015 [cited by applicant]
US 20150315569A1 · Weisinger et al. · 2015 [cited by applicant]
US 20150321164A1 · Li et al. · 2015 [cited by applicant]
US 20150344872A1 · Harbury et al. · 2015 [cited by applicant]
US 20160040158A1 · Wagner et al. · 2016 [cited by applicant]
US 20160222054A1 · Brown et al. · 2016 [cited by applicant]
US 20160314242A1 · Schnall-Levin et al. · 2016 [cited by applicant]
US 20160369267A1 · Wagner · 2016 [cited by applicant]
US 20170009225A1 · Franch et al. · 2017 [cited by applicant]
US 20170198336A1 · Reddavide et al. · 2017 [cited by applicant]
US 20180002688A1 · Keefe et al. · 2018 [cited by applicant]
US 20180135043A1 · Wong et al. · 2018 [cited by applicant]
US 20190112730A1 · He et al. · 2019 [cited by applicant]
US 20190136227A1 · Freskgard et al. · 2019 [cited by applicant]
US 20190169607A1 · Watts · 2019 [cited by applicant]
US 20200216836A1 · Franch et al. · 2020 [cited by applicant]
US 20200263163A1 · Watts et al. · 2020 [cited by applicant]
US 20200332441A1 · Watts et al. · 2020 [cited by applicant]
RU 2223319C1 · 2004 [cited by applicant]
WO WO2000023458A1 · 2000 [cited by applicant]
WO WO2001096335A1 · 2001 [cited by applicant]
WO WO2003078446A2 · 2003 [cited by applicant]
WO WO2004110964A2 · 2004 [cited by applicant]
WO WO2005003778A2 · 2005 [cited by applicant]
WO WO2006047791A2 · 2006 [cited by applicant]
WO WO2006079061A2 · 2006 [cited by applicant]
WO WO2007062664A3 · 2007 [cited by applicant]
WO WO2009077173A2 · 2009 [cited by applicant]
WO WO2009079624A1 · 2009 [cited by applicant]
WO WO2011127933A1 · 2011 [cited by applicant]
WO WO2012004204A1 · 2012 [cited by applicant]
WO WO2015021080A2 · 2015 [cited by applicant]
WO WO2015135856A1 · 2015 [cited by applicant]
WO WO2016025804A1 · 2016 [cited by applicant]
WO WO2016165621A1 · 2016 [cited by applicant]
WO WO2017062973A2 · 2017 [cited by applicant]
WO WO2017189631A2 · 2017 [cited by applicant]
WO WO2017218293A1 · 2017 [cited by applicant]
WO WO2018118897A1 · 2018 [cited by applicant]
WO WO2018166532A1 · 2018 [cited by applicant]
WO WO2018204420A1 · 2018 [cited by applicant]
WO WO2019060856A1 · 2019 [cited by applicant]
Abdel-Magid et al., (1996). “Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride,” J. Org. Chem., 61:3849-3862. [cited by applicant]
Artuso et al., (2007). “Preparation of mono-, di-, and trisubstituted ureas by carbonylation of aliphatic amines with 5,5-dimethyl dithiocarbonate,” Synthesis, 22:3497-3506. [cited by applicant]
Balcom et al., (1953). “Reductions with hydrazine hydrate catalyzed by Raney nickel,” J. Am. Chem. Soc., 76:4334. [cited by applicant]
Barrow et al., (2007). “Design and synthesis of 2,3,5-substituted imidazolidin-4-one inhibitors of BACE-I,” Chem. Med. Chem., 2:995-999. [cited by applicant]
Beugelmans et al., (1995). “Palladium catalyzed reductive deprotection of Alloc: Transprotection and peptide bond formation,” Tetrahedron Lett., 36:3129-3132. [cited by applicant]
Bikard et al., (2010). “Folded DNA in Action: Hairpin Formation and Biological Functions in Prokaryotes,” Microbiology And Molecular Biology Reviews, 74:570-588. [cited by applicant]
Brazda et al., (2011). “Cruciform structures are a common DNA feature important for regulating biological processes,” BMC Molecular Biology, 12:33, 16 pages. [cited by applicant]
Brenner et al., (1992). “Encoded combinatorial chemistry,” Proc Natl Acad Sci USA, 89(12):5381-5383. [cited by applicant]
Buller et al., (2008). “Design and synthesis of a novel DNA-encoded chemical library using Diels-Alder cycloadditions,” Biorganic & Medicinal Chemistry Letters, 18:5926-5931. [cited by applicant]
Carriero et al., (2003). “Template-Mediated Synthesis of Lariat RNA and DNA,” Journal of Organic Chemistry, 68:8328-8338. [cited by applicant]
Chauleta et al., (2011). “Design, synthesis and biological evaluation of new thalidomide analogues as TNF-a and IL-6 production inhibitors,” Bioorg. Med. Chem. Lett., 21:1019-1022. [cited by applicant]
Deprez-Poulain et al., (2007). “Convenient synthesis of 4H-1,2,4-triazole-3-thiols using di-2-pyridylthionocarbonate,” Tetrahedron Lett., 48:8157-8162. [cited by applicant]
Domaratzki, (2009). “Hairpin Structures Defined by DNA Trajectories,” Theory Comput Syst., 44:432-454. [cited by applicant]
Durand et al., (1990). “Circular dichroism studies of an oligodeoxyribonucleotide containing a hairpin loop made of a hexaethylene glycol chain: conformation and stability,” Nucleic acids research, 18:6353-6359. [cited by applicant]
Elia, (2010). “Protein Biotinylation,” Current Protocols in Protein Science, 3.6.1-3.6.21. [cited by applicant]
Fedorova et al., (1996). “Cyanogen Bromide-Induced Chemical Ligation: Mechanism and Optimization of the Reaction Conditions,” Nucleosides and Nucleotides, 15:1137-1147. [cited by applicant]
Franzini et.al., (2014). “Systematic Evaluation and Optimization of Modification Reactions of Oligonucleotides with Amines and Carboxylic Acids for the Synthesis of DNA-Encoded Chemical Libraries,” Bioconjugate Chemistr… [cited by applicant]
Giaever et al., (2002). “Functional profiling of the [cited by applicant]
Gryaznov et al., (1993). “Chemical ligation of oligonucleotides in the presence and absence of a template,” J. Am. Chem. Soc., 115:3808-3809. [cited by applicant]
Gurevich et al., (1991). “Preparative in vitro mRNA synthesis using SP6 and T7 RNA polymerases,” Analytical Biochemistry, 195:207-213. [cited by applicant]
Halpin et al., (2004). “DNA Display III. Solid Phase Organic Synthesis on Unprotected DNA,” PLoS Biology, 2(7):1031-1038. [cited by applicant]
Hong et al., (2009). “Analysis and Optimization of Copper-Catalyzed Azide-Alkyne Cycloaddition for Bioconjugation,” Angewandte Chem Int Ed Engl., 48:9879-9883, 13 pages. [cited by applicant]
Inglis et al., (2006). “Synthesis of N-benzylated-2-aminoquinolines as ligands for the Tec SH3 domain,” Bioorg. Med. Chem. Lett., 16:387-390. [cited by applicant]
Kanan et al., (2004). “Reaction discovery enabled by DNA-templated synthesis and in vitro selection,” Nature, 431:545-549. [cited by applicant]
Li et al., (2011). “Copper-free Sonogashira cross-coupling for functionalization of alkyne encoded proteins in aqueous medium and in bacterial cells,” J. Am. Chem. Soc., 133:15316-15319, 10 pages. [cited by applicant]
Liang et al., (2005). “Cooper-free 15 sonogashira coupling reaction with PdC12 in water under aerobic conditions,” J. Org. Chem., 70:391-393. [cited by applicant]
Lubbad et al., (2002). “Micropreparative fractionation of DNA fragments on metathesis-based monoliths: influence of stoichiometry on separation,” J Chromatogr A., 959(1-2):121-9. [cited by applicant]
Lubbad et al., (2011). “Ring-opening metathesis polymerization-derived monolithic anion exchangers for the fast separation of double-stranded DNA fragments,” J Chromatogr A., 1218(17):2362-7. [cited by applicant]
Lubbad et al., (2011). “Ring-opening metathesis polymerization-derived monolithic strong anion exchangers for the separation of 5'-phosphorylated oligodeoxythymidylic acids fragments,” J Chromatogr A., 1218(49):8897-902. [cited by applicant]
Mandal et al., (2014). “RIP3 induces apoptosis independent of pronecrotic kinase activity,” Mol. Cell, 56:481-495. [cited by applicant]
Manocci et al., (2011). “20 years of DNA-encoded chemical libraries,” Chem. Commun., 47:12747-12753. [cited by applicant]
Marziale et al., (2011). “An efficient protocol for copper-free 20 palladium-catalyzed Sonogashira crosscoupling in aqueous media at low temperatures,” Tetrahedron Lett., 52:6355-6358. [cited by applicant]
Mukhopadhyay et al., (2008). “Dowex 50W: A highly efficient and recyclable green catalyst for the construction of the 2-substituted benzimidazole moiety in aqueous medium,” Catal. Commun., 9:2392-2394. [cited by applicant]
Plieva et al., (2004). “Characterization of polyacrylamide based monolithic columns,” J. Sep. Sci., 27:828-836. [cited by applicant]
Plieva et al., (2006). “Macroporous polyacrylamide monolithic gels with immobilized metal affinity ligands: the effect of porous structure and ligand coupling chemistry on protein binding,” J. Mol. Recognit., 19:305-312. [cited by applicant]
Plieva et al., (2008). “Cryogel applications in microbiology,” Trends in Microbiology, 16(11):543-551. [cited by applicant]
Pokrovskaya et al., (1994). “In Vitro Transcription: Preparative RNA Yields in Analytical Scale Reactions,” Analytical Biochemistry, 220:420-423. [cited by applicant]
Potewar et al., (2008). “Catalyst-free efficient synthesis of 2-aminothiazoles in water at ambient temperature,” Tetrahedron 64:5019-5022. [cited by applicant]
Roughley et al., (2011). “The medicinal chemist's toolbox: an analysis of reactions used in the pursuit of drug candidates,” J. Med. Chem., 54:3451-3479. [cited by applicant]
Satz et al., (2015). “DNA Compatible Multistep Synthesis and Applications to DNA Encoded Libraries,” Bioconjugate Chemistry, 26(8):1623-1632. [cited by applicant]
Shabarova et al., (1991). “Chemical ligation of DNA: the first non-enzymatic assembly of a biologically active gene,” Nucleic Acids Research, 19:4247-4251. [cited by applicant]
Svoboda et al., (2006). “Hairpin RNA: a secondary structure of primary importance,” Cellular and Molecular Life Sciences, 63(7):901-908. [cited by applicant]
Wang et al., (2011). “Asymmetric synthesis of LFA-1 inhibitor B1RT2584 on metric ton scale,” Org. Process Res. Dev., 15:1185-1191. [cited by applicant]
Witt et al., (2000). “Synthesis and reactions of some 2-vinyl-3H-quinazolin-4-ones,” Tetrahedron, 56:7245-7253. [cited by applicant]
Xie et al., (1996). “Preparation of porous hydrophilic monoliths: Effect of the polymerization conditions on the porous properties of poly (acrylamide-co-N,N'-methylenebisacrylamide) monolithic rods,” J. Polym. Sci. A P… [cited by applicant]