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A DNA-encoded chemical library based on chiral 4-amino-proline enables stereospecific isozyme-selective protein recognition

Nature Chemistry volume 15, pages 1431–1443 (2023)Cite this article

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Abstract

DNA-encoded chemical libraries (DELs) consist of large chemical compound collections individually linked to DNA barcodes, facilitating pooled construction and screening. However, screening campaigns often fail if the molecular arrangement of the building blocks is not conducive to an efficient interaction with a protein target. Here we postulated that the use of rigid, compact and stereo-defined central scaffolds for DEL synthesis may facilitate the discovery of very specific ligands capable of discriminating between closely related protein targets. We synthesized a DEL comprising 3,735,936 members, featuring the four stereoisomers of 4-aminopyrrolidine-2-carboxylic acid as central scaffolds. The library was screened in comparative selections against pharmaceutically relevant targets and their closely related protein isoforms. Hit validation results revealed a strong impact of stereochemistry, with large affinity differences between stereoisomers. We identified potent isozyme-selective ligands against multiple protein targets. Some of these hits, specific to tumour-associated antigens, demonstrated tumour-selective targeting in vitro and in vivo. Collectively, constructing DELs with stereo-defined elements contributed to high library productivity and ligand selectivity.

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Fig. 1: Synthesis of SO-DEL.
Fig. 2: Identification and validation of CAIX ligands.
Fig. 3: Identification and validation of TNAP ligands.
Fig. 4: Identification and validation of PSMA ligands.
Fig. 5: Identification and validation of Nsp14 ligands.
Fig. 6: Identification and validation of HSA ligands.

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Data availability

All data supporting the findings of this study are available within the article and Supplementary Information. Next-generation sequencing data of all selection duplicates are provided as separate text files. Source Data Figs. 1–6 and Supplementary Figs. 14, 19, 20, 43–46 and 53–63 are provided with the paper. The Fastq file, containing raw high throughput Illumina sequence counts, is not provided in this article and Supplementary Information, but can be made available to readers upon justified request addressed to the corresponding authors. Source data are provided with this paper.

Code availability

Software for the evaluation of HTDS has previously been reported5.

References

  1. Hughes, J. P., Rees, S., Kalindjian, S. B. & Philpott, K. L. Principles of early drug discovery. Br. J. Pharmacol. 162, 1239–1249 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Macarron, R. et al. Impact of high-throughput screening in biomedical research. Nat. Rev. Drug Discov. 10, 188–195 (2011).

    Article  CAS  PubMed  Google Scholar 

  3. Goodnow, R. A., Dumelin, C. E. & Keefe, A. D. DNA-encoded chemistry: enabling the deeper sampling of chemical space. Nat. Rev. Drug Discov. 16, 131–147 (2017).

    Article  CAS  PubMed  Google Scholar 

  4. Neri, D. & Lerner, R. A. DNA-encoded chemical libraries: a selection system based on endowing organic compounds with amplifiable information. Annu. Rev. Biochem. 87, 479–502 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Decurtins, W. et al. Automated screening for small organic ligands using DNA-encoded chemical libraries. Nat. Protoc. 11, 764–780 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mannocci, L. et al. High-throughput sequencing allows the identification of binding molecules isolated from DNA-encoded chemical libraries. Proc. Natl Acad. Sci. USA 105, 17670–17675 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Buller, F. et al. Design and synthesis of a novel DNA-encoded chemical library using Diels–Alder cycloadditions. Bioorg. Med. Chem. Lett. 18, 5926–5931 (2008).

    Article  CAS  PubMed  Google Scholar 

  8. Clark, M. A. et al. Design, synthesis and selection of DNA-encoded small-molecule libraries. Nat. Chem. Biol. 5, 647–654 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Favalli, N. et al. Stereo- and regiodefined DNA-encoded chemical libraries enable efficient tumour-targeting applications. Nat. Chem. 13, 540–548 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Li, Y. et al. Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold. Nat. Chem. 10, 441–448 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gartner, Z. J. et al. DNA-templated organic synthesis and selection of a library of macrocycles. Science 305, 1601–1605 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li, Y., Zhao, P., Zhang, M., Zhao, X. & Li, X. Multistep DNA-templated synthesis using a universal template. J. Am. Chem. Soc. 135, 17727–17730 (2013).

    Article  CAS  PubMed  Google Scholar 

  13. Petersen, L. K. et al. Novel p38α MAP kinase inhibitors identified from yoctoReactor DNA-encoded small molecule library. MedChemComm 7, 1332–1339 (2016).

    Article  CAS  Google Scholar 

  14. Melkko, S., Scheuermann, J., Dumelin, C. E. & Neri, D. Encoded self-assembling chemical libraries. Nat. Biotechnol. 22, 568–574 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Wichert, M. et al. Dual-display of small molecules enables the discovery of ligand pairs and facilitates affinity maturation. Nat. Chem. 7, 241–249 (2015).

    Article  CAS  PubMed  Google Scholar 

  16. Reddavide, F. V., Lin, W., Lehnert, S. & Zhang, Y. DNA-encoded dynamic combinatorial chemical libraries. Angew. Chem. Int. Ed. 54, 7924–7928 (2015).

    Article  CAS  Google Scholar 

  17. Li, G. et al. Design, preparation, and selection of DNA-encoded dynamic libraries. Chem. Sci. 6, 7097–7104 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Litovchick, A. et al. Encoded library synthesis using chemical ligation and the discovery of sEH inhibitors from a 334-million member library. Sci Rep. 5, 10916 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bassi, G. et al. A single-stranded DNA-encoded chemical library based on a stereoisomeric scaffold enables ligand discovery by modular assembly of building blocks. Adv. Sci. 7, 2001970 (2020).

    Article  CAS  Google Scholar 

  20. Sannino, A. et al. Quantitative assessment of affinity selection performance using DNA-encoded chemical libraries. ChemBioChem 20, 955–962 (2018).

    Article  Google Scholar 

  21. Santos, R. et al. A comprehensive map of molecular drug targets. Nat. Rev. Drug Discov. 16, 19–34 (2017).

    Article  CAS  PubMed  Google Scholar 

  22. Huggins, D. J., Sherman, W. & Tidor, B. Rational approaches to improving selectivity in drug design. J. Med. Chem. 55, 1424–1444 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tafreshi, N. K., Lloyd, M. C., Bui, M. M., Gillies, R. J. & Morse, D. L. Carbonic anhydrase IX as an imaging and therapeutic target for tumors and metastases. Subcell. Biochem. 75, 221–254 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Aggarwal, M., Boone, C. D., Kondeti, B. & McKenna, R. Structural annotation of human carbonic anhydrases. J. Enzyme Inhib. Med. Chem. 28, 267–277 (2013).

    Article  PubMed  Google Scholar 

  25. Supuran, C. T. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov. 7, 168–181 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Cazzamalli, S., Dal Corso, A. & Neri, D. Acetazolamide serves as selective delivery vehicle for dipeptide-linked drugs to renal cell carcinoma. Mol. Cancer Ther. 15, 2926–2935 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kulterer, O. C. et al. A microdosing study with 99mTc-PHC-102 for the SPECT/CT imaging of primary and metastatic lesions in renal cell carcinoma patients. J. Nucl. Med. 62, 360 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhong, L. et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct. Target. Ther. 6, 201 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sartor, O. et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N. Engl. J. Med. 385, 1091–1103 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Heynickx, N., Herrmann, K., Vermeulen, K., Baatout, S. & Aerts, A. The salivary glands as a dose limiting organ of PSMA-targeted radionuclide therapy: a review of the lessons learnt so far. Nucl. Med. Biol. 98-99, 30–39 (2021).

    Article  CAS  PubMed  Google Scholar 

  31. Lucaroni, L. et al. Cross-reactivity to glutamate carboxypeptidase III causes undesired salivary gland and kidney uptake of PSMA-targeted small-molecule radionuclide therapeutics. Eur. J. Nucl. Med. Mol. Imaging 50, 957–961 (2023).

    Article  CAS  PubMed  Google Scholar 

  32. Bassi, G. et al. Specific inhibitor of placental alkaline phosphatase isolated from a DNA-encoded chemical library targets tumor of the female reproductive tract. J. Nucl. Med. 64, 15799–15809 (2021).

    CAS  Google Scholar 

  33. Gerry, C. J., Wawer, M. J., Clemons, P. A. & Schreiber, S. L. DNA barcoding a complete matrix of stereoisomeric small molecules. J. Am. Chem. Soc. 141, 10225–10235 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Benhamou, R. I. et al. DNA-encoded library versus RNA-encoded library selection enables design of an oncogenic noncoding RNA inhibitor. Proc. Natl Acad. Sci. USA 119, e2114971119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Favalli, N. et al. A DNA-encoded library of chemical compounds based on common scaffolding structures reveals the impact of ligand geometry on protein recognition. ChemMedChem 13, 1303–1307 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Levy, M. & Ellington, A. D. Directed evolution of streptavidin variants using in vitro compartmentalization. Chem. Biol. 15, 979–989 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Supuran, C. T., Briganti, F., Tilli, S., Chegwidden, W. R. & Scozzafava, A. Carbonic anhydrase inhibitors: sulfonamides as antitumor agents? Bioorg. Med. Chem. 9, 703–714 (2001).

    Article  CAS  PubMed  Google Scholar 

  38. Vintonyak, V. V., Antonchick, A. P., Rauh, D. & Waldmann, H. The therapeutic potential of phosphatase inhibitors. Curr. Opin. Chem. Biol. 13, 272–283 (2009).

    Article  CAS  PubMed  Google Scholar 

  39. Bigatti, M. et al. Impact of a central scaffold on the binding affinity of fragment pairs isolated from DNA-encoded self-assembling chemical libraries. ChemMedChem 12, 1748–1752 (2017).

    Article  CAS  PubMed  Google Scholar 

  40. Hoylaerts, M. F., Ding, L., Narisawa, S., Van kerckhoven, S. & Millán, J. L. Mammalian alkaline phosphatase catalysis requires active site structure stabilization via the N-terminal amino acid microenvironment. Biochemistry 45, 9756–9766 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Kramer, V. et al. Biodistribution and dosimetry of a single dose of albumin-binding ligand [(177)Lu]Lu-PSMA-ALB-56 in patients with mCRPC. Eur. J. Nucl. Med. Mol. Imaging 48, 893–903 (2021).

    Article  CAS  PubMed  Google Scholar 

  42. Lucaroni, L. et al. Cross-reactivity to glutamate carboxypeptidase III causes undesired salivary gland and kidney uptake of PSMA-targeted small molecule radionuclide therapeutics, Eur. J. Nucl. Med. Mol. Imaging (2022), in revision.

  43. Kelly, J. M. et al. Albumin-binding PSMA ligands: implications for expanding the therapeutic window. J. Nucl. Med. 60, 656 (2019).

    Article  CAS  PubMed  Google Scholar 

  44. Dumelin, C. E. et al. A portable albumin binder from a DNA-encoded chemical library. Angew. Chem. Int. Ed. 47, 3196–3201 (2008).

    Article  CAS  Google Scholar 

  45. Tan, D. S., Foley, M. A., Shair, M. D. & Schreiber, S. L. Stereoselective synthesis of over two million compounds having structural features both reminiscent of natural products and compatible with miniaturized cell-based assays. J. Am. Chem. Soc. 120, 8565–8566 (1998).

    Article  CAS  Google Scholar 

  46. Scott, K. A. et al. Stereochemical diversity as a source of discovery in chemical biology. Curr. Res. Chem. Biol. 2, 100028 (2022).

    Article  CAS  Google Scholar 

  47. Ferraroni, M., Cornelio, B., Sapi, J., Supuran, C. T. & Scozzafava, A. Sulfonamide carbonic anhydrase inhibitors: zinc coordination and tail effects influence inhibitory efficacy and selectivity for different isoforms. Inorg. Chim. Acta 470, 128–132 (2018).

    Article  CAS  Google Scholar 

  48. Cazzamalli, S., Corso, A. D. & Neri, D. Linker stability influences the anti-tumor activity of acetazolamide-drug conjugates for the therapy of renal cell carcinoma. J. Control. Release 246, 39–45 (2017).

    Article  PubMed  Google Scholar 

  49. Cazzamalli, S. et al. In vivo antitumor activity of a novel acetazolamide–cryptophycin conjugate for the treatment of renal cell carcinomas. ACS Omega 3, 14726–14731 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Pellegrino, C. et al. Impact of ligand size and conjugation chemistry on the performance of universal chimeric antigen receptor T-cells for tumor killing. Bioconjug. Chem. 31, 1775–1783 (2020).

    Article  CAS  PubMed  Google Scholar 

  51. Tölle, M., Reshetnik, A., Schuchardt, M., Höhne, M. & van der Giet, M. Arteriosclerosis and vascular calcification: causes, clinical assessment and therapy. Eur. J. Clin. Invest. 45, 976–985 (2015).

    Article  PubMed  Google Scholar 

  52. Opdebeeck, B. et al. Pharmacological TNAP inhibition efficiently inhibits arterial media calcification in a warfarin rat model but deserves careful consideration of potential physiological bone formation/mineralization impairment. Bone 137, 115392 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Safety profile. PLUVICTO https://www.hcp.novartis.com/products/pluvicto/psma-positive-mcrpc/safety-profile/ (2022).

  54. Kopka, K., Benešová, M., Bařinka, C., Haberkorn, U. & Babich, J. Glu-ureido–based inhibitors of prostate-specific membrane antigen: lessons learned during the development of a novel class of low-molecular-weight theranostic radiotracers. J. Nucl. Med. 58, 17S–26S (2017).

    Article  CAS  PubMed  Google Scholar 

  55. Srinivasarao, M., Galliford, C. V. & Low, P. S. Principles in the design of ligand-targeted cancer therapeutics and imaging agents. Nat. Rev. Drug Discov. 14, 203–219 (2015).

    Article  CAS  PubMed  Google Scholar 

  56. Stefanelli, P. & Rezza, G. COVID-19 vaccination strategies and their adaptation to the emergence of SARS-CoV-2 variants. Vaccines 10, 905 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Taylor, P. C. et al. Neutralizing monoclonal antibodies for treatment of COVID-19. Nat. Rev. Immunol. 21, 382–393 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Xiang, R. et al. Recent advances in developing small-molecule inhibitors against SARS-CoV-2. Acta Pharm. Sin. B 12, 1591–1623 (2022).

    Article  CAS  PubMed  Google Scholar 

  59. Owen, D. R. et al. An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19. Science 374, 1586–1593 (2021).

    Article  CAS  PubMed  Google Scholar 

  60. Minskaia, E. et al. Discovery of an RNA virus 3′→5′ exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc. Natl Acad. Sci. USA 103, 5108–5113 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Ma, Y. et al. Structural basis and functional analysis of the SARS coronavirus nsp14–nsp10 complex. Proc. Natl Acad. Sci. USA 112, 9436–9441 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ogando, N. S. et al. The enzymatic activity of the nsp14 exoribonuclease is critical for replication of MERS-CoV and SARS-CoV-2. J. Virol. 94, e01246–01220. (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Devkota, K. et al. Probing the SAM binding site of SARS-CoV-2 nsp14 in vitro using SAM competitive inhibitors guides developing selective bi-substrate inhibitors. SLAS Discov. 26, 1200–1211 (2021).

    Article  CAS  PubMed  Google Scholar 

  64. Otava, T. et al. The structure-based design of SARS-CoV-2 nsp14 methyltransferase ligands yields nanomolar inhibitors. ACS Infect. Dis. 7, 2214–2220 (2021).

    Article  CAS  PubMed  Google Scholar 

  65. Hofman, G.-J. et al. Minimising conformational bias in fluoroprolines through vicinal difluorination. Chem. Commun. 54, 5118–5121 (2018).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank A. Galbiati and A. Zana for the support with the in vivo experiments. Furthermore, the authors thank C. Pellegrino for the help with flow cytometry measurements. The authors received no specific funding for this work.

Author information

Authors and Affiliations

  1. Philochem AG, Otelfingen, Switzerland

    Sebastian Oehler, Laura Lucaroni, Francesca Migliorini, Abdullah Elsayed, Luca Prati, Sara Puglioli, Mattia Matasci, Samuele Cazzamalli, Dario Neri, Nicholas Favalli & Gabriele Bassi

  2. Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland

    Abdullah Elsayed, Kristina Schira, Jörg Scheuermann & Dario Neri

  3. Institute of Molecular Biology and Biophysics, Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland

    Denis Yudin, Min Jia & Nenad Ban

  4. NeoTX Therapeutics LTD, Stanford, CA, USA

    Dave Bushnell & Roger Kornberg

  5. Department of Structural Biology, Stanford University, Stanford, CA, USA

    Roger Kornberg

  6. Philogen SPA, Siena, Italy

    Dario Neri

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  1. Sebastian Oehler
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Contributions

All authors have contributed to the manuscript preparation (S. O., L. L., F. M., A. E., L. P., S. P., M. M., K. S., J. S., D. Y., M. J., N. B., D. B., R. K., S. C., D. N., N. F. and G. B.). S.O., G.B., N.F., S.C. and D.N. designed the experiments. S.O. synthesized the library with support from G.B., N.F. and F.M. S.O. and G.B. performed the selections. S.O., G.B., N.F. and J.S. analysed the HTS data. Hits were synthesized and validated by S.O. and G.B. with support from L.P., L.L., S.P., N.F. and A.E. A.E., L.L., S.O., M.M., L.P., G.B. and N.F. expressed and biotinylated the proteins with exception of Nsp14, which was provided by N.B., M.J., D.Y. and K.S. In vitro and in vivo experiments were performed by S.O., G.B. and S.C.

Corresponding authors

Correspondence to Nicholas Favalli or Gabriele Bassi.

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Competing interests

D.N. is co-founder, CEO, CSO and President of the Scientific Advisory Board of Philogen. S.O., L.L., A.E., F.M., S.P., M.M., L.P., S.C., N.F. and G.B. are employed by Philochem AG, the research and development unit of the Philogen. R.K. is member of the Board of Directors Chair and Scientific Advisory Board of NeoTX Therapeutics LTD. D.B. is CSO of the Discovery Division at NeoTX Therapeutics LTD. All other authors do not declare any conflict of interest.

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Nature Chemistry thanks Christian Heinis and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Table 1 Chemical structures of the linkers used for the in vitro and in vivo validation of SO-DEL hit compounds
Full size table

Supplementary information

Supplementary Information

Supplementary Figs. 1–279, Supplementary Tables 1–7, results, experimental data, procedural details, synthesis and characterization data, NMR spectra, mass spectrometry spectra and source data files.

Reporting Summary

Supplementary Table 1

Source data file for supplementary figures.

Supplementary Data 1

Next-generation sequencing raw data of all selection duplicates are provided as separate text files.

Source data

Source Data Fig. 2

Numerical source data of FP measurements, SPR sensograms, affinity constant values and quantitative biodistributions.

Source Data Fig. 3

Numerical source data of FP measurements.

Source Data Fig. 4

Numerical source data of FP measurements and of the co-elution experiment.

Source Data Fig. 4

Unprocessed microscope image of immunofluorescence staining of human submandibular salivary glands with PSMA-617*.

Source Data Fig. 4

Unprocessed microscope image of immunofluorescence staining of human submandibular salivary glands with compound 45.

Source Data Fig. 5

Numerical source data of FP measurements.

Source Data Fig. 6

Numerical source data of FP measurements and affinity constant values.

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Oehler, S., Lucaroni, L., Migliorini, F. et al. A DNA-encoded chemical library based on chiral 4-amino-proline enables stereospecific isozyme-selective protein recognition. Nat. Chem. 15, 1431–1443 (2023). https://doi.org/10.1038/s41557-023-01257-3

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