An Integrated Microfluidic Processor for DNA-Encoded Combinatorial Library Functional Screening

ACS Combinatorial Science

Volumn 19, Issue 3, 2017, Pages 181-192

  MacConnell, Andrew B ^a   Price, Alexander K ^a   Paegel, Brian M ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

combinatorial compound libraries; DNA encoded synthesis; miniaturized automation

Indexed keywords

CATHEPSIN D; DNA; ENZYME INHIBITOR; MICROSPHERE; PEPSTATIN;

ANTAGONISTS AND INHIBITORS; CHEMISTRY; COMBINATORIAL CHEMISTRY; DEVICES; EQUIPMENT DESIGN; GENE LIBRARY; HUMAN; LAB ON A CHIP; NUCLEOTIDE SEQUENCE; PRECLINICAL STUDY;

BASE SEQUENCE; CATHEPSIN D; COMBINATORIAL CHEMISTRY TECHNIQUES; DNA; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; EQUIPMENT DESIGN; GENE LIBRARY; HUMANS; LAB-ON-A-CHIP DEVICES; MICROSPHERES; PEPSTATINS;

EID: 85017505688     PISSN: 21568952     EISSN: 21568944     Source Type: Journal    
DOI: 10.1021/acscombsci.6b00192     Document Type: Article

References (64)

1. Gartner, Z. J.; Liu, D. R. The Generality of DNA-Templated Synthesis as a Basis for Evolving Non-Natural Small Molecules J. Am. Chem. Soc. 2001, 123, 6961-6963 10.1021/ja015873n
2. Halpin, D. R.; Harbury, P. B. DNA Display I. Sequence-Encoded Routing of DNA Populations PLoS Biol. 2004, 2, E173 10.1371/journal.pbio.0020173
3. Melkko, S.; Scheuermann, J.; Dumelin, C.; Neri, D. Encoded Self-Assembling Chemical Libraries Nat. Biotechnol. 2004, 22, 568-574 10.1038/nbt961
4. Clark, M. A.; Acharya, R. A.; Arico-Muendel, C. C.; Belyanskaya, S. L.; Benjamin, D. R.; Carlson, N. R.; Centrella, P. A.; Chiu, C. H.; Creaser, S. P.; Cuozzo, J. W. et al. Design, Synthesis and Selection of DNA-Encoded Small-Molecule Libraries Nat. Chem. Biol. 2009, 5, 647-654 10.1038/nchembio.211
5. Brenner, S.; Lerner, R. A. Encoded Combinatorial Chemistry Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 5381-5383 10.1073/pnas.89.12.5381
6. Smith, G. P. Filamentous Fusion Phage: Novel Expression Vectors That Display Cloned Antigens on the Virion Surface Science 1985, 228, 1315-1317 10.1126/science.4001944
7. Hanes, J.; Pluckthun, A. In Vitro Selection and Evolution of Functional Proteins by Using Ribosome Display Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 4937-4942 10.1073/pnas.94.10.4937
8. Roberts, R. W.; Szostak, J. W. RNA-Peptide Fusions for the in Vitro Selection of Peptides and Proteins Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 12297-12302 10.1073/pnas.94.23.12297
9. Ding, Y.; Clark, M. A. Robust Suzuki-Miyaura Cross-Coupling on DNA-Linked Substrates ACS Comb. Sci. 2015, 17, 1-4 10.1021/co5001037
10. Satz, A. L.; Cai, J.; Chen, Y.; Goodnow, R.; Gruber, F.; Kowalczyk, A.; Petersen, A.; Naderi-Oboodi, G.; Orzechowski, L.; Strebel, Q. DNA Compatible Multistep Synthesis and Applications to DNA Encoded Libraries Bioconjugate Chem. 2015, 26, 1623-1632 10.1021/acs.bioconjchem.5b00239
11. Eidam, O.; Satz, A. L. Analysis of the Productivity of DNA Encoded Libraries MedChemComm 2016, 7, 1323-1331 10.1039/C6MD00221H
12. Disch, J. S.; Evindar, G.; Chiu, C. H.; Blum, C. A.; Dai, H.; Jin, L.; Schuman, E.; Lind, K. E.; Belyanskaya, S. L.; Deng, J. et al. Discovery of Thieno[3,2-D]Pyrimidine-6-Carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3 J. Med. Chem. 2013, 56, 3666-3679 10.1021/jm400204k
13. Encinas, L.; O’Keefe, H.; Neu, M.; Remuiñán, M. J.; Patel, A. M.; Guardia, A.; Davie, C. P.; Pérez-Macías, N.; Yang, H.; Convery, M. A. et al. Encoded Library Technology as a Source of Hits for the Discovery and Lead Optimization of a Potent and Selective Class of Bactericidal Direct Inhibitors of Mycobacterium Tuberculosis InhA J. Med. Chem. 2014, 57, 1276-1288 10.1021/jm401326j
14. Deng, H.; Zhou, J.; Sundersingh, F. S.; Summerfield, J.; Somers, D.; Messer, J. A.; Satz, A. L.; Ancellin, N.; Arico-Muendel, C. C.; Sargent Bedard, K. L. et al. Discovery, SAR, and X-Ray Binding Mode Study of BCATm Inhibitors From a Novel DNA-Encoded Library ACS Med. Chem. Lett. 2015, 6, 919-924 10.1021/acsmedchemlett.5b00179
15. Wu, Z.; Graybill, T. L.; Zeng, X.; Platchek, M.; Zhang, J.; Bodmer, V. Q.; Wisnoski, D. D.; Deng, J.; Coppo, F. T.; Yao, G. et al. Cell-Based Selection Expands the Utility of DNA-Encoded Small-Molecule Library Technology to Cell Surface Drug Targets: Identification of Novel Antagonists of the NK3 Tachykinin Receptor ACS Comb. Sci. 2015, 17, 722-731 10.1021/acscombsci.5b00124
16. Satz, A. L. DNA Encoded Library Selections and Insights Provided by Computational Simulations ACS Chem. Biol. 2015, 10, 2237-2245 10.1021/acschembio.5b00378
17. Beaudry, A. A.; Joyce, G. F. Science 1992, 257, 635-641 10.1126/science.1496376
18. Tawfik, D. S.; Griffiths, A. Man-Made Cell-Like Compartments for Molecular Evolution Nat. Biotechnol. 1998, 16, 652-656 10.1038/nbt0798-652
19. Blakskjær, P.; Heitner, T.; Hansen, N. J. V. Fidelity by Design: Yoctoreactor and Binder Trap Enrichment for Small-Molecule DNA-Encoded Libraries and Drug Discovery Curr. Opin. Chem. Biol. 2015, 26, 62-71 10.1016/j.cbpa.2015.02.003
20. Furka, A.; Sebestyen, F.; Asgedom, M.; Dibo, G. General-Method for Rapid Synthesis of Multicomponent Peptide Mixtures Int. J. Pept. Protein Res. 1991, 37, 487-493 10.1111/j.1399-3011.1991.tb00765.x
21. Houghten, R. A.; Pinilla, C.; Blondelle, S. E.; Appel, J. R.; Dooley, C. T.; Cuervo, J. H. Generation and Use of Synthetic Peptide Combinatorial Libraries for Basic Research and Drug Discovery Nature 1991, 354, 84-86 10.1038/354084a0
22. Lam, K. S.; Salmon, S. E.; Hersh, E. M.; Hruby, V. J.; Kazmierski, W. M.; Knapp, R. J. A New Type of Synthetic Peptide Library for Identifying Ligand-Binding Activity Nature 1991, 354, 82-84 10.1038/354082a0
23. Silen, J. L.; Lu, A. T.; Solas, D. W.; Gore, M. A.; Maclean, D.; Shah, N. H.; Coffin, J. M.; Bhinderwala, N. S.; Wang, Y. W.; Tsutsui, K. T. et al. Screening for Novel Antimicrobials From Encoded Combinatorial Libraries by Using a Two-Dimensional Agar Format Antimicrob. Agents Chemother. 1998, 42, 1447-1453
24. Blackwell, H. E.; Pérez, L.; Stavenger, R. A.; Tallarico, J. A.; Cope Eatough, E.; Foley, M. A.; Schreiber, S. L. A One-Bead, One-Stock Solution Approach to Chemical Genetics: Part 1 Chem. Biol. 2001, 8, 1167-1182 10.1016/S1074-5521(01)00085-0
25. You, A. J.; Jackman, R. J.; Whitesides, G. M.; Schreiber, S. L. A Miniaturized Arrayed Assay Format for Detecting Small Molecule-Protein Interactions in Cells Chem. Biol. 1997, 4, 969-975 10.1016/S1074-5521(97)90305-7
26. Upert, G.; Merten, C. A.; Wennemers, H. Nanoliter Plates-Versatile Tools for the Screening of Split-and-Mix Libraries on-Bead and Off-Bead Chem. Commun. 2010, 46, 2209-2211 10.1039/b927017e
27. Borchardt, A.; Liberles, S.; Biggar, S.; Crabtree, G.; Schreiber, S. Small Molecule-Dependent Genetic Selection in Stochastic Nanodroplets as a Means of Detecting Protein-Ligand Interactions on a Large Scale Chem. Biol. 1997, 4, 961-968 10.1016/S1074-5521(97)90304-5
28. Thorsen, T.; Roberts, R.; Arnold, F.; Quake, S. Dynamic Pattern Formation in a Vesicle-Generating Microfluidic Device Phys. Rev. Lett. 2001, 86, 4163-4166 10.1103/PhysRevLett.86.4163
29. Anna, S.; Bontoux, N.; Stone, H. Formation of Dispersions Using “Flow Focusing” in Microchannels Appl. Phys. Lett. 2003, 82, 364-366 10.1063/1.1537519
30. Song, H.; Tice, J.; Ismagilov, R. A Microfluidic System for Controlling Reaction Networks in Time Angew. Chem., Int. Ed. 2003, 42, 768-772 10.1002/anie.200390203
31. Song, H.; Chen, D. L.; Ismagilov, R. F. Reactions in Droplets in Microfluidic Channels Angew. Chem., Int. Ed. 2006, 45, 7336-7356 10.1002/anie.200601554
32. Baret, J.-C.; Miller, O. J.; Taly, V.; Ryckelynck, M.; El-Harrak, A.; Frenz, L.; Rick, C.; Samuels, M. L.; Hutchison, J. B.; Agresti, J. J. et al. Fluorescence-Activated Droplet Sorting (FADS): Efficient Microfluidic Cell Sorting Based on Enzymatic Activity Lab Chip 2009, 9, 1850-1858 10.1039/b902504a
33. Sciambi, A.; Abate, A. R. Accurate Microfluidic Sorting of Droplets at 30 kHz Lab Chip 2015, 15, 47-51 10.1039/C4LC01194E
34. Christopher, G. F.; Bergstein, J.; End, N. B.; Poon, M.; Nguyen, C.; Anna, S. L. Coalescence and Splitting of Confined Droplets at Microfluidic Junctions Lab Chip 2009, 9, 1102-1109 10.1039/b813062k
35. Frenz, L.; Blank, K.; Brouzes, E.; Griffiths, A. D. Reliable Microfluidic on-Chip Incubation of Droplets in Delay-Lines Lab Chip 2009, 9, 1344-1348 10.1039/B816049J
36. Frenz, L.; Blouwolff, J.; Griffiths, A. D.; Baret, J.-C. Microfluidic Production of Droplet Pairs Langmuir 2008, 24, 12073-12076 10.1021/la801954w
37. Xu, L.; Lee, H.; Panchapakesan, R.; Oh, K. W. Fusion and Sorting of Two Parallel Trains of Droplets Using a Railroad-Like Channel Network and Guiding Tracks Lab Chip 2012, 12, 3936-3942 10.1039/c2lc40456g
38. Chen, D.; Liu, Y.; Liu, W.; Kuznetsov, A.; Mendez, F. E.; Philipson, L. H.; Ismagilov, R. F. et al. The Chemistrode: a Droplet-Based Microfluidic Device for Stimulation and Recording with High Temporal, Spatial, and Chemical Resolution Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 16843-16848 10.1073/pnas.0807916105
39. Sun, S.; Slaney, T. R.; Kennedy, R. T. Label Free Screening of Enzyme Inhibitors at Femtomole Scale Using Segmented Flow Electrospray Ionization Mass Spectrometry Anal. Chem. 2012, 84, 5794-5800 10.1021/ac3011389
40. Price, A. K.; MacConnell, A. B.; Paegel, B. M. Microfluidic Bead Suspension Hopper Anal. Chem. 2014, 86, 5039-5044 10.1021/ac500693r
41. Courtois, F.; Olguin, L. F.; Whyte, G.; Bratton, D.; Huck, W. T. S.; Abell, C.; Hollfelder, F. An Integrated Device for Monitoring Time-Dependent in Vitro Expression From Single Genes in Picolitre Droplets ChemBioChem 2008, 9, 439-446 10.1002/cbic.200700536
42. Mazutis, L.; Baret, J.-C.; Treacy, P.; Skhiri, Y.; Araghi, A. F.; Ryckelynck, M.; Taly, V.; Griffiths, A. D. Multi-Step Microfluidic Droplet Processing: Kinetic Analysis of an in Vitro Translated Enzyme Lab Chip 2009, 9, 2902-2908 10.1039/b907753g
43. Fallah-Araghi, A.; Baret, J.-C.; Ryckelynck, M.; Griffiths, A. D. A Completely in Vitro Ultrahigh-Throughput Droplet-Based Microfluidic Screening System for Protein Engineering and Directed Evolution Lab Chip 2012, 12, 882-891 10.1039/c2lc21035e
44. Autour, A.; Westhof, E.; Ryckelynck, M. iSpinach: a Fluorogenic RNA Aptamer Optimized for in Vitro Applications Nucleic Acids Res. 2016, 44, 2491-2500 10.1093/nar/gkw083
45. Price, A. K.; Paegel, B. M. Discovery in Droplets Anal. Chem. 2016, 88, 339-353 10.1021/acs.analchem.5b04139
46. Price, A. K.; MacConnell, A. B.; Paegel, B. M. hνSABR: Photochemical Dose-Response Bead Screening in Droplets Anal. Chem. 2016, 88, 2904-2911 10.1021/acs.analchem.5b04811
47. Sciambi, A.; Abate, A. R. Generating Electric Fields in PDMS Microfluidic Devices with Salt Water Electrodes Lab Chip 2014, 14, 2605-2609 10.1039/c4lc00078a
48. MacConnell, A. B.; McEnaney, P. J.; Cavett, V. J.; Paegel, B. M. DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis ACS Comb. Sci. 2015, 17, 518-534 10.1021/acscombsci.5b00106
49. Mendes, K. R.; Malone, M. L.; Ndungu, J. M.; Suponitsky-Kroyter, I.; Cavett, V. J.; McEnaney, P. J.; MacConnell, A. B.; Doran, T. M.; Ronacher, K.; Stanley, K. et al. High-Throughput Identification of DNA-Encoded IgG Ligands That Distinguish Active and Latent Mycobacterium Tuberculosis Infections ACS Chem. Biol. 2017, 12, 234-243 10.1021/acschembio.6b00855
50. Appell, K. C.; Chung, T. D. Y.; Ohlmeyer, M. J. H.; Sigal, N. H.; Baldwin, J. J.; Chelsky, D. Biological Screening of a Large Combinatorial Library J. Biomol. Screening 1996, 1, 27-31 10.1177/108705719600100111
51. Doran, T. M.; Gao, Y.; Mendes, K.; Dean, S.; Simanski, S.; Kodadek, T. Utility of Redundant Combinatorial Libraries in Distinguishing High and Low Quality Screening Hits ACS Comb. Sci. 2014, 16, 259-270 10.1021/co500030f
52. Zhang, J.; Chung, T.; Oldenburg, K. A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays J. Biomol. Screening 1999, 4, 67-73 10.1177/108705719900400206
53. Sun, S.; Kennedy, R. T. Droplet Electrospray Ionization Mass Spectrometry for High-Throughput Screening for Enzyme Inhibitors Anal. Chem. 2014, 86, 9309-9314 10.1021/ac502542z
54. Knight, C. G.; Barrett, A. J. Interaction of Human Cathepsin D with the Inhibitor Pepstatin Biochem. J. 1976, 155, 117-125 10.1042/bj1550117
55. Macosko, E. Z.; Basu, A.; Satija, R.; Nemesh, J.; Shekhar, K.; Goldman, M.; Tirosh, I.; Bialas, A. R.; Kamitaki, N.; Martersteck, E. M. et al. Highly Parallel Genome-Wide Expression Profiling of Individual Cells Using Nanoliter Droplets Cell 2015, 161, 1202-1214 10.1016/j.cell.2015.05.002
56. Klein, A. M.; Mazutis, L.; Akartuna, I.; Tallapragada, N.; Veres, A.; Li, V.; Peshkin, L.; Weitz, D. A.; Kirschner, M. W. Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells Cell 2015, 161, 1187-1201 10.1016/j.cell.2015.04.044
57. Malone, M. L.; Paegel, B. M. What Is a “DNA-Compatible” Reaction? ACS Comb. Sci. 2016, 18, 182-187 10.1021/acscombsci.5b00198
58. Gossett, D. R.; Tse, H. T. K.; Lee, S. A.; Ying, Y.; Lindgren, A. G.; Yang, O. O.; Rao, J.; Clark, A. T.; Di Carlo, D. Hydrodynamic Stretching of Single Cells for Large Population Mechanical Phenotyping Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 7630-7635 10.1073/pnas.1200107109
59. Qvortrup, K.; Nielsen, T. E. In-Bead Screening of Hydroxamic Acids for the Identification of HDAC Inhibitors Angew. Chem., Int. Ed. 2016, 55, 4472-4475 10.1002/anie.201511308
60. Lian, W.; Upadhyaya, P.; Rhodes, C. A.; Liu, Y.; Pei, D. Screening Bicyclic Peptide Libraries for Protein-Protein Interaction Inhibitors: Discovery of a Tumor Necrosis Factor-A Antagonist J. Am. Chem. Soc. 2013, 135, 11990-11995 10.1021/ja405106u
61. Trinh, T. B.; Upadhyaya, P.; Qian, Z.; Pei, D. Discovery of a Direct Ras Inhibitor by Screening a Combinatorial Library of Cell-Permeable Bicyclic Peptides ACS Comb. Sci. 2016, 18, 75-85 10.1021/acscombsci.5b00164
62. Choi, J.-W.; Kim, G.-J.; Lee, S.; Kim, J.; deMello, A. J.; Chang, S.-I. A Droplet-Based Fluorescence Polarization Immunoassay (dFPIA) Platform for Rapid and Quantitative Analysis of Biomarkers Biosens. Bioelectron. 2015, 67, 497-502 10.1016/j.bios.2014.09.013
63. Chan, T. R.; Hilgraf, R.; Sharpless, K. B.; Fokin, V. V. Polytriazoles as Copper(I)-Stabilizing Ligands in Catalysis Org. Lett. 2004, 6, 2853-2855 10.1021/ol0493094
64. Duffy, D.; McDonald, J.; Schueller, O.; Whitesides, G. Anal. Chem. (Washington, DC, U. S.) 1998, 70, 4974-4984 10.1021/ac980656z