Amplifiable Novel DNA-Encoded Chemical Libraries on Drug Discovery

Saidarao Korampalli

doi:10.37022/jcscr.v2i1.599

Korampalli Saidarao Priyadarshini Institute of Pharmaceutical Education and Research, 5th mile, Pulladigunta-522017, Guntur, Andhra Pradesh. India.

DOI https://doi.org/10.37022/jcscr.v2i1.599

Abstract

The development of DNA-Encoded Chemical Libraries (DELs) has accelerated recently due to the identification of tiny ligands, and the majority of major pharmaceutical companies have adopted the technique. An important issue in biology, chemistry, and the biomedical sciences is the development of chemical ligands that bind to proteins with specificity. By encoding individual organic compounds with unique DNA tags that function as amplifiable identifying bar codes, it is possible to create and transfer unprecedentedly large combinatorial libraries, which in turn makes it easier to find ligands for a wide range of protein targets. Fundamentally, chemical synthesis and genetic abilities are linked. Several experimental implementations of the technique have been reduced to preparation since the first description of DNA-encoded chemical libraries was published in 1992. As a result, a number of ideal DELs with the highest possible percentage of biologically significant chemotypes were selected, each of which covered the chemical space of ChEMBL to the fullest extent. A series of mutually complimentary libraries that enable even greater coverage of ChEMBL than is achievable with a single DEL were discovered through the analysis of various DEL combinations.Keywords: ILD, Infection, fibrotic pattern, respiratory tract.

Keywords: DNA-Encoded chemical library, small molecule drug discovery, libraries design and comparison, hit identification, drug discovery, drug design, combinatorial chemistry

References

1. Folmer RH. Integrating biophysics with HTS-driven drug discovery projects. Drug Discovery Today. 2016 Mar 1;21(3):491-8.
2. Schreiber SL. Target-oriented and diversity-oriented organic synthesis in drug discovery. Science. 2000 Mar 17;287(5460):1964-9.
3. McCafferty J, Griffiths AD, Winter G, Chiswell DJ. Phage antibodies: filamentous phage displaying antibody variable domains. nature. 1990 Dec 6;348(6301):552-4.
4. Hwisa NT, Katakam P, Chandu BR, Ismael MH, Bader A. Pandemic influenza A (H1N1) vaccination among libyan health care personnel: A cross-sectional retrospective study. Journal of Pharmacy and Bioallied sciences. 2014 Jul 1;6(3):192-7.
5. Jespers LS, Roberts A, Mahler SM, Winter G, Hoogenboom HR. Guiding the selection of human antibodies from phage display repertoires to a single epitope of an antigen. Bio/technology. 1994 Sep 1;12(9):899-903.
6. Katakam P, Dey B, Assaleh FH, Hwisa NT, Adiki SK, Chandu BR, Mitra A. Top-down and bottom-up approaches in 3D printing technologies for drug delivery challenges. Critical Reviews™ in Therapeutic Drug Carrier Systems. 2015;32(1).
7. Gura T. DNA helps build molecular libraries for drug testing.
8. Bharatia R, Kumar S, Chaursiya S, Gautam KM, Bharti S, Varun R. Sphingosomes: A Novel Vesicular Drug Delivery System. International Journal of Pharma Professional’s Research (IJPPR). 2023;14(3):88-93.
9. Sun CP, Zhang XY, Morisseau C, Hwang SH, Zhang ZJ, Hammock BD, Ma XC. Discovery of Soluble Epoxide Hydrolase Inhibitors from Chemical Synthesis and Natural Products. J Med Chem. 2021 Jan 14;64(1):184-215. doi: 10.1021/acs.jmedchem.0c01507. Epub 2020 Dec 28. PMID: 33369424; PMCID: PMC7942193.
10. Martini RP, Siler D, Cetas J, Alkayed NJ, Allen E, Treggiari MM. A double-blind, randomized, placebo-controlled trial of soluble epoxide hydrolase inhibition in patients with aneurysmal subarachnoid hemorrhage. Neurocritical Care. 2022 Jun 1:1-1.
11. Harris PA, King BW, Bandyopadhyay D, Berger SB, Campobasso N, Capriotti CA, Cox JA, Dare L, Dong X, Finger JN, Grady LC. DNA-encoded library screening identifies benzo [b][1, 4] oxazepin-4-ones as highly potent and monoselective receptor interacting protein 1 kinase inhibitors. Journal of medicinal chemistry. 2016 Mar 10;59(5):2163-78.
12. Weisel K, Berger S, Thorn K, Taylor PC, Peterfy C, Siddall H, Tompson D, Wang S, Quattrocchi E, Burriss SW, Walter J. A randomized, placebo-controlled experimental medicine study of RIPK1 inhibitor GSK2982772 in patients with moderate to severe rheumatoid arthritis. Arthritis research & therapy. 2021 Dec;23:1-2.
13. Kumar KR, Nagaraju GV, Subrahmanyam SN, Nagarani K, Shareef S, Tennygilphin M, Namballa M. Assessment on Elements Involving the Academic Performance among Pharmacy Students: A Cross-Sectional Observational Study. Int J Cur Res Rev| Vol. 2021 Dec;13(23):141.
14. Ge R, Shen Z, Yin J, Chen W, Zhang Q, An Y, Tang D, Satz AL, Su W, Kuai L. Discovery of SARS-CoV-2 main protease covalent inhibitors from a DNA-encoded library selection. Slas Discovery. 2022 Mar 1;27(2):79-85.
15. Wichert M, Krall N, Decurtins W, Franzini RM, Pretto F, Schneider P, Neri D, Scheuermann J. Dual-display of small molecules enables the discovery of ligand pairs and facilitates affinity maturation. Nature chemistry. 2015 Mar;7(3):241-9.
16. Kulterer OC, Pfaff S, Wadsak W, Garstka N, Remzi M, Vraka C, Nics L, Mitterhauser M, Bootz F, Cazzamalli S, Krall N. A microdosing study with 99mTc-PHC-102 for the SPECT/CT imaging of primary and metastatic lesions in renal cell carcinoma patients. Journal of Nuclear Medicine. 2021 Mar 1;62(3):360-5.
17. Salamon H, Klika Škopić M, Jung K, Bugain O, Brunschweiger A. Chemical biology probes from advanced DNA-encoded libraries. ACS Chemical Biology. 2016 Feb 19;11(2):296-307.
18. Goodnow Jr RA, Dumelin CE, Keefe AD. DNA-encoded chemistry: enabling the deeper sampling of chemical space. Nature Reviews Drug Discovery. 2017 Feb;16(2):131-47.
19. Ravella S, Angel M, Subramanian H, Thangavel N, Namballa M, Lokesh D, Mishra AK, Nagaraju GV. Navigating the Future of Cancer Diagnosis: A Comprehensive Review of Novel Approaches for Community-Based Treatment. future.;1:6.
20. Blakskjaer P, Heitner T, Hansen NJ. Fidelity by design: Yoctoreactor and binder trap enrichment for small-molecule DNA-encoded libraries and drug discovery. Current Opinion in Chemical Biology. 2015 Jun 1;26:62-71.
21. Clark MA, Acharya RA, Arico-Muendel CC, Belyanskaya SL, Benjamin DR, Carlson NR, Centrella PA, Chiu CH, Creaser SP, Cuozzo JW, Davie CP. Design, synthesis and selection of DNA-encoded small-molecule libraries. Nature chemical biology. 2009 Sep;5(9):647-54.
22. Buller F, Mannocci L, Zhang Y, Dumelin CE, Scheuermann J, Neri D. Design and synthesis of a novel DNA-encoded chemical library using Diels-Alder cycloadditions. Bioorganic & medicinal chemistry letters. 2008 Nov 15;18(22):5926-31.