Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia

Nature Chemistry

Volumn 8, Issue 1, 2016, Pages 24-32

  Li, Hongyu ^a   Valkenier, Hennie ^a   Judd, Luke W ^a   Brotherhood, Peter R ^a   Hussain, Sabir ^a   Cooper, James A ^a   Jurček, Ondřej ^a,b   Sparkes, Hazel A ^a   Sheppard, David N ^a   Davis, Anthony P ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b UNIVERSITY OF JYVÄSKYLÄ   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

1-PALMITOYL-2-OLEOYLPHOSPHATIDYLCHOLINE; ANION; BACTERIAL PROTEIN; CHLORINE; CYCLOHEXANE DERIVATIVE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DECALIN; DRUG CARRIER; NAPHTHALENE DERIVATIVE; PHOSPHATIDYLCHOLINE; PHOTOPROTEIN; STEROID; YELLOW FLUORESCENT PROTEIN, BACTERIA;

ANIMAL; CELL MEMBRANE; CELL PROLIFERATION; CELL SURVIVAL; CHEMICAL STRUCTURE; CHEMISTRY; DOG; DRUG DESIGN; DRUG EFFECTS; ELECTROPHYSIOLOGY; EPITHELIUM CELL; FISCHER 344 RAT; FLUORESCENCE MICROSCOPY; GENETICS; HELA CELL LINE; HUMAN; HYDROGEN BOND; ION TRANSPORT; MDCK CELL LINE; METABOLISM;

ANIMALS; ANIONS; BACTERIAL PROTEINS; CELL MEMBRANE; CELL PROLIFERATION; CELL SURVIVAL; CHLORINE; CYCLOHEXANES; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DOGS; DRUG CARRIERS; DRUG DESIGN; ELECTROPHYSIOLOGICAL PHENOMENA; EPITHELIAL CELLS; HELA CELLS; HUMANS; HYDROGEN BONDING; ION TRANSPORT; LUMINESCENT PROTEINS; MADIN DARBY CANINE KIDNEY CELLS; MICROSCOPY, FLUORESCENCE; MOLECULAR STRUCTURE; NAPHTHALENES; PHOSPHATIDYLCHOLINES; RATS, INBRED F344; STEROIDS;

EID: 84950997466     PISSN: 17554330     EISSN: 17554349     Source Type: Journal    
DOI: 10.1038/nchem.2384     Document Type: Article

References (47)

1. Sessler, J. L. & Allen, W. E. Anion carriers: new tools for crossing membranes. Chemtech. 29, 16-24 (1999).
2. Davis, A. P., Sheppard, D. N. & Smith, B. D. Development of synthetic membrane transporters for anions. Chem. Soc. Rev. 36, 348-357 (2007).
3. Davis, J. T., Okunola, O. & Quesada, R. Recent advances in the transmembrane transport of anions. Chem. Soc. Rev. 39, 3843-3862 (2010).
4. Busschaert, N. & Gale, P. A. Small-molecule lipid-bilayer anion transporters for biological applications. Angew. Chem. Int. Ed. 52, 1374-1382 (2013).
5. Pressman, B. C. Biological applications of ionophores. Ann. Rev. Biochem. 45, 501-530 (1976).
6. Dutton, C. J., Banks, B. J. & Cooper, C. B. Polyether ionophores. Nat. Prod. Rep. 12, 165-181 (1995).
7. Vargas Jentzsch, A., Hennig, A., Mareda, J. & Matile, S. Synthetic ion transporters that work with anion-π interactions, halogen bonds, and anion-macrodipole interactions. Acc. Chem. Res. 46, 2791-2800 (2013).
8. Gale, P. A., Perez-Tomas, R. & Quesada, R. Anion transporters and biological systems. Acc. Chem. Res. 46, 2801-2813 (2013).
9. Gokel, G. W. & Negin, S. Synthetic ion channels: from pores to biological applications. Acc. Chem. Res. 46, 2824-2833 (2013).
10. Valkenier, H. & Davis, A. P. Making a match for valinomycin: steroidal scaffolds in the design of electroneutral, electrogenic anion carriers. Acc. Chem. Res. 46, 2898-2909 (2013).
11. + channels. Biochim. Biophys. Acta 1464, 69-82 (2000).
12. Ashcroft, F. M. Ion Channels and Disease (Academic Press, 2000).
13. Stoltz, D. A., Meyerholz, D. K. & Welsh, M. J. Origins of cystic fibrosis lung disease. N. Engl. J. Med. 372, 351-362 (2015).
14. - secretion in cystic fibrosis epithelial cells by an analog of squalamine. Am. J. Physiol. Lung Cell Mol. Physiol. 281, L1164-L1172 (2001).
15. Broughman, J. R. et al. Distinct structural elements that direct solution aggregation and membrane assembly in the channel-forming peptide M2GlyR. Biochemistry 41, 7350-7358 (2002).
16. Broughman, J. R. et al. Channel-forming peptide modulates transepithelial electrical conductance and solute permeability. Am. J. Physiol. Cell Physiol. 286, C1312-C1323 (2004).
17. Pajewski, R. et al. A synthetic, chloride-selective channel that alters chloride transport in epithelial cells. Chem. Commun. 329-331 (2006).
18. Koulov, A. V. et al. Chloride transport across vesicle and cell membranes by steroid-based receptors. Angew. Chem. Int. Ed. 42, 4931-4933 (2003).
19. Shen, B., Li, X., Wang, F., Yao, X. Q. & Yang, D. A synthetic chloride channel restores chloride conductance in human cystic fibrosis epithelial cells. PLoS ONE 7, e34694 (2012).
20. Sidorov, V. et al. Ion channel formation from a calix 4 arene amide that binds HCl. J. Am. Chem. Soc. 124, 2267-2278 (2002).
21. Sessler, J. L. et al. Synthesis, anion-binding properties, and in vitro anticancer activity of prodigiosin analogues. Angew. Chem. Int. Ed. 44, 5989-5992 (2005).
22. de Grenu, B. D. et al. Synthetic prodiginine obatoclax (GX15-070) and related analogues: anion binding, transmembrane transport, and cytotoxicity properties. Chem. Eur. J. 17, 14074-14083 (2011).
23. Busschaert, N. et al. Structure-activity relationships in tripodal transmembrane anion transporters: the effect of fluorination. J. Am. Chem. Soc. 133, 14136-14148 (2011).
24. Moore, S. J. et al. Chloride, carboxylate and carbonate transport by ortho-phenylenediamine-based bisureas. Chem. Sci. 4, 103-117 (2013).
25. Ko, S. K. et al. Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells. Nature Chem. 6, 885-892 (2014).
26. Davis, J. T. Anion binding and transport by prodigiosin and its analogs. Top. Heterocyclic Chem. 24, 145-176 (2010).
27. Brotherhood, P. R. & Davis, A. P. Steroid-based anion receptors and transporters. Chem. Soc. Rev. 39, 3633-3647 (2010).
28. McNally, B. A. et al. Structure-activity relationships in cholapod anion carriers: enhanced transmembrane chloride transport through substituent tuning. Chem. Eur. J. 14, 9599-9606 (2008).
29. Edwards, S. J., Valkenier, H., Busschaert, N., Gale, P. A. & Davis, A. P. High affinity anion binding by steroidal squaramide receptors. Angew. Chem. Int. Ed. 54, 4592-4596 (2015).
30. Hussain, S., Brotherhood, P. R., Judd, L. W. & Davis, A. P. Diaxial diureido decalins as compact, efficient, and tunable anion transporters. J. Am. Chem. Soc. 133, 1614-1617 (2011).
31. Valkenier, H. et al. Preorganized bis-thioureas as powerful anion carriers: chloride transport by single molecules in large unilamellar vesicles. J. Am. Chem. Soc. 136, 12507-12512 (2014).
32. Cooper, J. A., Street, S. T. G. & Davis, A. P. A flexible solution to anion transport: powerful anionophores based on a cyclohexane scaffold. Angew. Chem. Int. Ed. 53, 5609-5613 (2014).
33. McNally, B. A., Koulov, A. V., Smith, B. D., Joos, J. B. & Davis, A. P. A fluorescent assay for chloride transport; identification of a synthetic anionophore with improved activity. Chem. Commun. 1087-1089 (2005).
34. Clare, J. P. et al. Substrate discrimination by cholapod anion receptors: geometric effects and the 'affinity-selectivity principle'. J. Am. Chem. Soc. 127, 10739-10746 (2005).
35. Li, X., Shen, B., Yao, X. Q. & Yang, D. A small synthetic molecule forms chloride channels to mediate chloride transport across cell membranes. J. Am. Chem. Soc. 129, 7264-7265 (2007).
36. Verkman, A. S. & Galietta, L. J. V. Chloride channels as drug targets. Nature Rev. Drug Discov. 8, 153-171 (2009).
37. Galietta, L. J. V., Haggie, P. M. & Verkman, A. S. Green fluorescent protein-based halide indicators with improved chloride and iodide affinities. FEBS Lett. 499, 220-224 (2001).
38. Sheppard, D. N., Carson, M. R., Ostedgaard, L. S., Denning, G. M. & Welsh, M. J. Expression of cystic fibrosis transmembrane conductance regulator in a model epithelium. Am. J. Physiol. Lung Cell. Mol. Physiol. 266, L405-L413 (1994).
39. Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug. Deliv. Rev. 46, 3-26 (2001).
40. Cutting, G. R. Cystic fibrosis genetics: from molecular understanding to clinical application. Nature Rev. Genet. 16, 45-56 (2015).
41. Alton, E. W. F. W. et al. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. Respir. Med. 3, 684-691 (2015).
42. Ramsey, B. W. et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N. Engl. J. Med. 365, 1663-1672 (2011).
43. Wainwright, C. E. et al. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N. Engl. J. Med. 373, 220-231 (2015).
44. Mall, M. A. & Galietta, L. J. V. Targeting ion channels in cystic fibrosis. J. Cyst. Fibros. 14, 561-570 (2015).
45. McLachlan, G. et al. Optimizing aerosol gene delivery and expression in the ovine lung. Mol. Ther. 15, 348-354 (2007).
46. Galietta, L. V. J., Jayaraman, S. & Verkman, A. S. Cell-based assay for highthroughput quantitative screening of CFTR chloride transport agonists. Am. J. Physiol. Cell Physiol. 281, C1734-C1742 (2001).
47. - secretion, and renal cyst growth: a study using CFTR inhibitors. Kidney Int. 66, 1926-1938 (2004).