Skip to main content
SpringerLink
Log in
Book cover

Thermodynamics and Biophysics of Biomedical Nanosystems pp 339–364Cite as

Drug-Membrane Interactions in the Renin Angiotensin System

  • Chapter
  • First Online:

Part of the book series: Series in BioEngineering ((SERBIOENG))

Abstract

Renin Angiotensin System (RAS) plays a key role in the pathophysiology of the cardiovascular and renal system. Within this system stimulation of the G-protein coupled receptor (GPCR) AT1 by the peptide angiotensin II (AII) has a central role. Molecules have been discovered which either block the formation of AII or compete with the activation of the AT1 receptor. Angiotensin Receptor Blockers (ARBs) or sartans are the first synthetic drugs of the latter class. Up to now the question has not been answered how the drug molecules reach the receptor site. Are these molecules incorporated in the lipid bilayers core before they freely diffuse to reach the active site or do they enter at the receptor binding site directly from the water phase? Both mechanisms are possible and may have a synergistic action. Various biophysical techniques, such as calorimetric, spectroscopic and X-ray scattering methods can provide valuable information on the dynamic and thermodynamic changes caused when drugs are incorporated into the lipid bilayers. Molecular Dynamics (MD) simulations are a valuable tool to acquire atomic level information on the molecular basis of the interaction between the drugs and the RAS system. The purpose of this chapter is to review the contribution of the various biophysical techniques and MD on drug-membrane interactions on the RAS system. Studies described in the manuscript are mainly referred to drugs acting on the GPCR AT1 receptor, however it is envisaged that the discussed concepts of drug interaction can apply also to other GPCRs.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Laragh, J.H., Baer, L., Brunner, H.R., Buhler, F.R., Vaughan, J.E.: Renin, angiotensin and aldosterone system in pathogenesis and management of hypertensive vascular disease. Am. J. Med. 52(5), 633–652 (1972). https://doi.org/10.1016/0002-9343(72)90054-X

    Article  Google Scholar 

  2. Zhang, H., Unal, H., Gati, C., Han, G.W., Liu, W., Zatsepin, N.A., James, D., Wang, D., Nelson, G., Weierstall, U., Sawaya, M.R., Xu, Q., Messerschmidt, M., Williams, G.J., Boutet, S., Yefanov, O.M., White, T.A., Wang, C., Ishchenko, A., Tirupula, K.C., Desnoyer, R., Coe, J., Conrad, C.E., Fromme, P., Stevens, R.C., Katritch, V., Karnik, S.S., Cherezov, V.: Structure of the Angiotensin receptor revealed by serial femtosecond crystallography. Cell 161(4), 833–844 (2015). https://doi.org/10.1016/j.cell.2015.04.011

    Article  Google Scholar 

  3. Nirula, V., Zheng, W., Sothinathan, R., Sandberg, K.: Interaction of biphenylimidazole and imidazoleacrylic acid nonpeptide antagonists with valine 108 in TM III of the AT1 angiotensin receptor. Br. J. Pharmacol. 119(8), 1505–1507 (1996)

    Article  Google Scholar 

  4. Dascal, D., Nirula, V., Lawus, K., Yoo, S.E., Walsh, T.F., Sandberg, K.: Shared determinants of receptor binding for subtype selective, and dual endothelin-angiotensin antagonists on the AT1 angiotensin II receptor. FEBS Lett. 423(1), 15–18 (1998)

    Article  Google Scholar 

  5. Ji, H., Zheng, W., Zhang, Y., Catt, K.J., Sandberg, K.: Genetic transfer of a nonpeptide antagonist binding site to a previously unresponsive angiotensin receptor. Proc. Natl. Acad. Sci. U S A 92(20), 9240–9244 (1995)

    Article  Google Scholar 

  6. Sakarellos, C., Lintner, K., Piriou, F., Fermandjian, S.: Conformation of the central sequence of angiotensin II and analogs. Biopolymers 22(2), 663–687 (1983). https://doi.org/10.1002/bip.360220210

    Article  Google Scholar 

  7. Balakumar, P., Jagadeesh, G.: Structural determinants for binding, activation, and functional selectivity of the angiotensin AT1 receptor. J. Mol. Endocrinol. 53(2), R71–92 (2014). https://doi.org/10.1530/jme-14-0125

    Article  Google Scholar 

  8. Leonis, G., Avramopoulos, A., Salmas, R.E., Durdagi, S., Yurtsever, M., Papadopoulos, M.G.: Elucidation of conformational states, dynamics, and mechanism of binding in human κ-opioid receptor complexes. J. Chem. Inf. Model. 54(8), 2294–2308 (2014). https://doi.org/10.1021/ci5002873

    Article  Google Scholar 

  9. Dror, R.O., Pan, A.C., Arlow, D.H., Borhani, D.W., Maragakis, P., Shan, Y., Xu, H., Shaw, D.E.: Pathway and mechanism of drug binding to G-protein-coupled receptors. Proc. Natl. Acad. Sci. U S A 108(32), 13118–13123 (2011). https://doi.org/10.1073/pnas.1104614108

    Article  Google Scholar 

  10. Shan, Y., Kim, E.T., Eastwood, M.P., Dror, R.O., Seeliger, M.A., Shaw, D.E.: How does a drug molecule find its target binding site? J. Am. Chem. Soc. 133(24), 9181–9183 (2011). https://doi.org/10.1021/ja202726y

    Article  Google Scholar 

  11. Rhodes, D.G., Sarmiento, J.G., Herbette, L.G.: Kinetics of binding of membrane-active drugs to receptor sites. Diffusion-limited rates for a membrane bilayer approach of 1,4-dihydropyridine calcium channel antagonists to their active site. Mol. Pharmacol. 27(6), 612–623 (1985)

    Google Scholar 

  12. Kellici, T.F., Ntountaniotis, D., Kritsi, E., Zervou, M., Zoumpoulakis, P., Potamitis, C., Durdagi, S., Salmas, R.E., Ergun, G., Gokdemir, E., Halabalaki, M., Gerothanassis, I.P., Liapakis, G., Tzakos, A., Mavromoustakos, T.: Leveraging NMR and X-ray data of the free ligands to build better drugs targeting Angiotensin II Type 1 G-protein coupled receptor. Curr. Med. Chem. 23(1), 36–59 (2016)

    Article  Google Scholar 

  13. Kellici, T.F., Ntountaniotis, D., Leonis, G., Chatziathanasiadou, M., Chatzikonstantinou, A.V., Becker-Baldus, J., Glaubitz, C., Tzakos, A.G., Viras, K., Chatzigeorgiou, P., Tzimas, S., Kefala, E., Valsami, G., Archontaki, H., Papadopoulos, M.G., Mavromoustakos, T.: Investigation of the interactions of silibinin with 2-hydroxypropyl-beta-cyclodextrin through biophysical techniques and computational methods. Mol. Pharm. 12(3), 954–965 (2015). https://doi.org/10.1021/mp5008053

    Article  Google Scholar 

  14. Ntountaniotis, D., Kellici, T., Tzakos, A., Kolokotroni, P., Tselios, T., Becker-Baldus, J., Glaubitz, C., Lin, S., Makriyannis, A., Mavromoustakos, T.: The application of solid-state NMR spectroscopy to study candesartan cilexetil (TCV-116) membrane interactions. Comparative study with the AT1R antagonist drug olmesartan. Biochim. Biophys. Acta 1838(10), 2439–2450 (2014). https://doi.org/10.1016/j.bbamem.2014.06.003

    Article  Google Scholar 

  15. Kellici, T.F., Tzakos, A.G., Mavromoustakos, T.: Rational drug design and synthesis of molecules targeting the angiotensin II type 1 and type 2 receptors. Molecules 20(3), 3868–3897 (2015). https://doi.org/10.3390/molecules20033868

    Article  Google Scholar 

  16. Kellici, T., Ntountaniotis, D., Vrontaki, E., Liapakis, G., Moutevelis-Minakakis, P., Kokotos, G., Hadjikakou, S.G., Tzakos, A., Afantitis, A., Melagraki, G., Bryant, S., Langer, T., Di Marzo, V., Mavromoustakos, T.: Rational drug design paradigms: the Odyssey for designing better drugs. Comb. Chem. High Throughput Screen. 18(3), 238–256 (2015)

    Google Scholar 

  17. Kellici, T.F., Ntountaniotis, D., Liapakis, G., Tzakos, A.G., Mavromoustakos, T.: The dynamic properties of angiotensin II type 1 receptor inverse agonists in solution and in the receptor site. Arab. J. Chem. (2016). https://doi.org/10.1016/j.arabjc.2016.11.014

  18. Moschonas, I.C., Kellici, T.F., Mavromoustakos, T., Stathopoulos, P., Tsikaris, V., Magafa, V., Tzakos, A.G., Tselepis, A.D.: Molecular requirements involving the human platelet protease-activated receptor-4 mechanism of activation by peptide analogues of its tethered-ligand. Platelets, 1–10 (2017). https://doi.org/10.1080/09537104.2017.1282607

    Article  Google Scholar 

  19. Zervou, M., Cournia, Z., Potamitis, C., Patargias, G., Durdagi, S., Grdadolnik, S.G.: Mavromoustakos T (2014) Insights into the molecular basis of action of the AT1 antagonist losartan using a combined NMR spectroscopy and computational approach. Biochim. Biophys. Acta 3, 1031–1046 (1838). https://doi.org/10.1016/j.bbamem.2013.12.012

    Article  Google Scholar 

  20. Zhang, H., Unal, H., Desnoyer, R., Han, G.W., Patel, N., Katritch, V., Karnik, S.S., Cherezov, V., Stevens, R.C.: Structural basis for ligand recognition and functional selectivity at angiotensin receptor. J. Biol. Chem. 290(49), 29127–29139 (2015). https://doi.org/10.1074/jbc.M115.689000

    Article  Google Scholar 

  21. Oliveira, T.R., Lamy, M.T., De Paula, U.M., Guimaraes, L.L., Toledo, M.S., Takahashi, H.K., Straus, A.H., Lindsey, C.J., Paiva, T.B.: Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes. Braz. J. Med. Biol. Res. 42(9), 844–853 (2009)

    Article  Google Scholar 

  22. Netticadan, T.J., Ashavaid, T.F., Nair, K.G.: Characterisation of the canine cardiac sarcolemma in experimental myocardial ischemia. Indian J. Clin. Biochem. 12(1), 49–54 (1997). https://doi.org/10.1007/BF02867955

    Article  Google Scholar 

  23. Vist, M.R., Davis, J.H.: Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine mixtures: 2H nuclear magnetic resonance and differential scanning calorimetry. Biochemistry 29(2), 451–464 (1990)

    Article  Google Scholar 

  24. Marsh, D.: Liquid-ordered phases induced by cholesterol: a compendium of binary phase diagrams. Biochim. Biophys. Acta 1798(3), 688–699 (2010). https://doi.org/10.1016/j.bbamem.2009.12.027

    Article  Google Scholar 

  25. Lingwood, D., Simons, K.: Lipid rafts as a membrane-organizing principle. Science 327(5961), 46–50 (2010). https://doi.org/10.1126/science.1174621

    Article  Google Scholar 

  26. Zoumpoulakis, P., Daliani, I., Zervou, M., Kyrikou, I., Siapi, E., Lamprinidis, G., Mikros, E., Mavromoustakos, T.: Losartan’s molecular basis of interaction with membranes and AT1 receptor. Chem. Phys. Lipids 125(1), 13–25 (2003)

    Article  Google Scholar 

  27. Fotakis, C., Christodouleas, D., Chatzigeorgiou, P., Zervou, M., Benetis, N.P., Viras, K., Mavromoustakos, T.: Development of a CP 31P NMR broadline simulation methodology for studying the interactions of antihypertensive AT1 antagonist losartan with phospholipid bilayers. Biophys. J. 96(6), 2227–2236 (2009). https://doi.org/10.1016/j.bpj.2008.11.057

    Article  Google Scholar 

  28. Theodoropoulou, E., Marsh, D.: Interactions of angiotensin II non-peptide AT(1) antagonist losartan with phospholipid membranes studied by combined use of differential scanning calorimetry and electron spin resonance spectroscopy. Biochim. Biophys. Acta 1461(1), 135–146 (1999)

    Article  Google Scholar 

  29. Schneider, M.F., Marsh, D., Jahn, W., Kloesgen, B., Heimburg, T.: Network formation of lipid membranes: triggering structural transitions by chain melting. Proc. Natl. Acad. Sci. U S A 96(25), 14312–14317 (1999)

    Article  Google Scholar 

  30. Estep, T.N., Mountcastle, D.B., Biltonen, R.L., Thompson, T.E.: Studies on the anomalous thermotropic behavior of aqueous dispersions of dipalmitoylphosphatidylcholine-cholesterol mixtures. Biochemistry 17(10), 1984–1989 (1978)

    Article  Google Scholar 

  31. Bruggemann, E.P., Melchior, D.L.: Alterations in the organization of phosphatidylcholine/cholesterol bilayers by tetrahydrocannabinol. J. Biol. Chem. 258(13), 8298–8303 (1983)

    Google Scholar 

  32. Mavromoustakos, T., Yang, D.P., Makriyannis, A.: Effects of the anesthetic steroid alphaxalone and its inactive delta 16-analog on the thermotropic properties of membrane bilayers. A model for membrane perturbation. Biochim. Biophys. Acta 1239(2), 257–264 (1995)

    Google Scholar 

  33. O’Leary, T.J., Levin, I.W.: Raman spectroscopic study of an interdigitated lipid bilayer. Dipalmitoylphosphatidylcholine dispersed in glycerol. Biochim. Biophys. Acta 776(2), 185–189 (1984)

    Google Scholar 

  34. Hsu, J.C., Yip, C.M.: Molecular dynamics simulations of indolicidin association with model lipid bilayers. Biophys. J. 92(12), L100–102 (2007). https://doi.org/10.1529/biophysj.107.108050

    Article  Google Scholar 

  35. Tian, X., Pavlopoulos, S., Yang, D.P., Makriyannis, A.: The interaction of cannabinoid receptor agonists, CP55940 and WIN55212-2 with membranes using solid state 2H NMR. Biochim. Biophys. Acta 1808(9), 2095–2101 (2011). https://doi.org/10.1016/j.bbamem.2010.11.026

    Article  Google Scholar 

  36. Ntountaniotis, D., Mali, G., Grdadolnik, S.G., Halabalaki, M., Skaltsounis, A.L., Potamitis, C., Siapi, E., Chatzigeorgiou, P., Rappolt, M., Mavromoustakos, T.: Thermal, dynamic and structural properties of drug AT1 antagonist olmesartan in lipid bilayers. Biochim. Biophys. Acta 1808(12), 2995–3006 (2011). https://doi.org/10.1016/j.bbamem.2011.08.001

    Article  Google Scholar 

  37. Mavromoustakos, T., Theodoropoulou, E., Yang, D.P.: The use of high-resolution solid-state NMR spectroscopy and differential scanning calorimetry to study interactions of anaesthetic steroids with membrane. Biochim. Biophys. Acta 1328(1), 65–73 (1997)

    Article  Google Scholar 

  38. Yang, D.P., Mavromoustakos, T., Beshah, K., Makriyannis, A.: Amphipathic interactions of cannabinoids with membranes. A comparison between Δ8-THC and its O-methyl analog using differential scanning calorimetry, X-ray diffraction and solid state 2H-NMR. BBA—Biomembr. 1103(1), 25–36 (1992). https://doi.org/10.1016/0005-2736(92)90053-o

    Article  Google Scholar 

  39. Mavromoustakos, T., Theodoropoulou, E.: A combined use of 13C-cross polarization/magic angle spinning, 13C-magic angle spinning and 31P-nuclear magnetic resonance spectroscopy with differential scanning calorimetry to study cannabinoid-membrane interactions. Chem. Phys. Lipids 92(1), 37–52 (1998). https://doi.org/10.1016/S0009-3084(98)00005-X

    Article  Google Scholar 

  40. Mavromoustakos, T., Daliani, I.: Effects of cannabinoids in membrane bilayers containing cholesterol. Biochim. Biophys. Acta 1420(1–2), 252–265 (1999)

    Article  Google Scholar 

  41. Santos, J.S., Lee, D.K., Ramamoorthy, A.: Effects of antidepressants on the conformation of phospholipid headgroups studied by solid-state NMR. Magn. Reson. Chem. 42(2), 105–114 (2004). https://doi.org/10.1002/mrc.1327

    Article  Google Scholar 

  42. O’Leary, T.J., Ross, P.D., Levin, I.W.: Effects of anesthetic and nonanesthetic steroids on dipalmitoylphosphatidylcholine liposomes: a calorimetric and Raman spectroscopic investigation. Biochemistry 23(20), 4636–4641 (1984)

    Article  Google Scholar 

  43. Potamitis, C., Chatzigeorgiou, P., Siapi, E., Viras, K., Mavromoustakos, T., Hodzic, A., Pabst, G., Cacho-Nerin, F., Laggner, P.: Rappolt M (2011) Interactions of the AT1 antagonist valsartan with dipalmitoyl-phosphatidylcholine bilayers. Biochim. Biophys. Acta 6, 1753–1763 (1808). https://doi.org/10.1016/j.bbamem.2011.02.002

    Article  Google Scholar 

  44. Colthup, N.B., Daly, L.H., Wiberley, S.E.: Introduction to Infrared and Raman Spectroscopy, 3rd edn. Academic Press, Boston (1990)

    Google Scholar 

  45. Levin, I.W., Lewis, E.N.: Fourier transform Raman spectroscopy of biological materials. Anal. Chem. 62(21), 1101A–1111A (1990)

    Google Scholar 

  46. Bista, R.K., Bruch, R.F., Covington, A.M.: Variable-temperature Raman spectro-microscopy for a comprehensive analysis of the conformational order in PEGylated lipids. J. Raman Spectrosc. 40(4), 463–471 (2009). https://doi.org/10.1002/jrs.2156

    Article  Google Scholar 

  47. Gaber, B.P., Peticolas, W.L.: On the quantitative interpretation of biomembrane structure by Raman spectroscopy. Biochim. Biophys. Acta 465(2), 260–274 (1977)

    Article  Google Scholar 

  48. Benetis, N.-P., Kyrikou, I., Zervou, M., Mavromoustakos, T.: Static CP 31P NMR multilamellar bilayer broadlines in the absence and presence of the bioactive dipeptide β-Ala-Tyr or Glu. Chem. Phys. 314(1–3), 57–72 (2005). https://doi.org/10.1016/j.chemphys.2005.01.028

    Article  Google Scholar 

  49. Kyrikou, I., Hadjikakou, S.K., Kovala-Demertzi, D., Viras, K., Mavromoustakos, T.: Effects of non-steroid anti-inflammatory drugs in membrane bilayers. Chem. Phys. Lipids 132(2), 157–169 (2004). https://doi.org/10.1016/j.chemphyslip.2004.06.005

    Article  Google Scholar 

  50. Michel, M.C., Foster, C., Brunner, H.R., Liu, L.: A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists. Pharmacol. Rev. 65(2), 809–848 (2013). https://doi.org/10.1124/pr.112.007278

    Article  Google Scholar 

  51. Tosco, P., Rolando, B., Fruttero, R., Henchoz, Y., Martel, S., Carrupt, P.A., Gasco, A.: Physicochemical profiling of sartans: a detailed study of ionization constants and distribution coefficients. Helv. Chim. Acta 91(3), 468–482 (2008). https://doi.org/10.1002/hlca.200890051

    Article  Google Scholar 

  52. Kritsi, E., Potamitis, C., Durdagi, S., Zoumpoulakis, P., Golic Grdadolnik, S., Mavromoustakos, T.: Molecular insights into the AT1 antagonism based on biophysical and in silico studies of telmisartan. Med. Chem. Res. 22(10), 4842–4857 (2013). https://doi.org/10.1007/s00044-012-0464-5

    Article  Google Scholar 

  53. Liossi, A.S., Ntountaniotis, D., Kellici, T.F., Chatziathanasiadou, M.V., Megariotis, G., Mania, M., Becker-Baldus, J., Kriechbaum, M., Krajnc, A., Christodoulou, E., Glaubitz, C., Rappolt, M., Amenitsch, H., Mali, G., Theodorou, D.N., Valsami, G., Pitsikalis, M., Iatrou, H., Tzakos, A.G.: Mavromoustakos T (2017) Exploring the interactions of irbesartan and irbesartan-2-hydroxypropyl-beta-cyclodextrin complex with model membranes. Biochim. Biophys. Acta 6, 1089–1098 (1859). https://doi.org/10.1016/j.bbamem.2017.03.003

    Article  Google Scholar 

  54. Bocskei, Z., Simon, K., Rao, R., Caron, A., Rodger, C.A., Bauer, M.: Irbesartan Crystal Form B. Acta Crystallogr Sect C: Cryst. Struct. Commun. 54(6), 808–810 (1998). doi:https://doi.org/10.1107/s0108270197019884

    Article  Google Scholar 

  55. Sadeghpour, A., Rappolt, M., Ntountaniotis, D., Chatzigeorgiou, P., Viras, K., Megariotis, G., Papadopoulos, M.G., Siapi, E., Mali, G.: Mavromoustakos T (2015) Comparative study of interactions of aliskiren and AT1 receptor antagonists with lipid bilayers. Biochim. Biophys. Acta 4, 984–994 (1848). https://doi.org/10.1016/j.bbamem.2014.12.004

    Article  Google Scholar 

  56. Ivetac, A., Andrew McCammon, J.: Mapping the druggable allosteric space of G-Protein coupled receptors: a fragment-based molecular dynamics approach. Chem. Biol. Drug Des. 76(3), 201–217 (2010). https://doi.org/10.1111/j.1747-0285.2010.01012.x

    Article  Google Scholar 

  57. Gkeka, P., Eleftheratos, S., Kolocouris, A., Cournia, Z.: Free energy calculations reveal the origin of binding preference for aminoadamantane blockers of influenza A/M2TM pore. J. Chem. Theory Comput. 9(2), 1272–1281 (2013). https://doi.org/10.1021/ct300899n

    Article  Google Scholar 

  58. Vanni, S., Neri, M., Tavernelli, I., Rothlisberger, U.: Predicting novel binding modes of agonists to β adrenergic receptors using all-atom molecular dynamics simulations. PLoS Comp. Biol. 7(1) (2011). https://doi.org/10.1371/journal.pcbi.1001053

    Article  Google Scholar 

  59. Gkeka, P., Sarkisov, L.: Interactions of phospholipid bilayers with several classes of amphiphilic α-helical peptides: insights from coarse-grained molecular dynamics simulations. J. Phys. Chem. B 114(2), 826–839 (2010). https://doi.org/10.1021/jp908320b

    Article  Google Scholar 

  60. Gkeka, P., Papafotika, A., Christoforidis, S., Cournia, Z.: Exploring a Non-ATP pocket for potential allosteric modulation of PI3 Kα. J. Phys. Chem. B 119(3), 1002–1016 (2015). https://doi.org/10.1021/jp506423e

    Article  Google Scholar 

  61. Cournia, Z., Allen, T.W., Andricioaei, I., Antonny, B., Baum, D., Brannigan, G., Buchete, N.V., Deckman, J.T., Delemotte, L., Del Val, C., Friedman, R., Gkeka, P., Hege, H.C., Henin, J., Kasimova, M.A., Kolocouris, A., Klein, M.L., Khalid, S., Lemieux, M.J., Lindow, N., Roy, M., Selent, J., Tarek, M., Tofoleanu, F., Vanni, S., Urban, S., Wales, D.J., Smith, J.C., Bondar, A.N.: Membrane protein structure, function, and dynamics: a perspective from experiments and theory. J. Membr. Biol. 248(4), 611–640 (2015). https://doi.org/10.1007/s00232-015-9802-0

    Article  Google Scholar 

  62. Periole, X., Huber, T., Marrink, S.-J., Sakmar, T.P.: G protein-coupled receptors self-assemble in dynamics simulations of model bilayers. J. Am. Chem. Soc. 129(33), 10126–10132 (2007). https://doi.org/10.1021/ja0706246

    Article  Google Scholar 

  63. Periole, X., Knepp, A.M., Sakmar, T.P., Marrink, S.J., Huber, T.: Structural determinants of the supramolecular organization of G protein-coupled receptors in bilayers. J. Am. Chem. Soc. 134(26), 10959–10965 (2012). https://doi.org/10.1021/ja303286e

    Article  Google Scholar 

  64. Filizola, M., Wang, S.X., Weinstein, H.: Dynamic models of G-protein coupled receptor dimers: indications of asymmetry in the rhodopsin dimer from molecular dynamics simulations in a POPC bilayer. J. Comput. Aided Mol. Des. 20(7), 405–416 (2006). https://doi.org/10.1007/s10822-006-9053-3

    Article  Google Scholar 

  65. Ísberg, V., Balle, T., Sander, T., Jørgensen, F.S., Gloriam, D.E.: G protein- and agonist-bound Serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations. J. Chem. Inf. Model. 51(2), 315–325 (2011). https://doi.org/10.1021/ci100402f

    Article  Google Scholar 

  66. Kruse, A.C., Hu, J., Pan, A.C., Arlow, D.H., Rosenbaum, D.M., Rosemond, E., Green, H.F., Liu, T., Chae, P.S., Dror, R.O., Shaw, D.E., Weis, W.I., Wess, J., Kobilka, B.K.: Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature 482(7386), 552–556 (2012)

    Article  Google Scholar 

  67. Mavromoustakos, T., Durdagi, S., Koukoulitsa, C., Simcic, M., Papadopoulos, M.G., Hodoscek, M., Grdadolnik, S.G.: Strategies in the rational drug design. Curr. Med. Chem. 18(17), 2517–2530 (2011)

    Article  Google Scholar 

  68. Topiol, S., Sabio, M.: X-ray structure breakthroughs in the GPCR transmembrane region. Biochem. Pharmacol. 78(1), 11–20 (2009). https://doi.org/10.1016/j.bcp.2009.02.012

    Article  Google Scholar 

  69. Congreve, M., Langmead, C.J., Mason, J.S., Marshall, F.H.: Progress in structure based drug design for G protein-coupled receptors. J. Med. Chem. 54(13), 4283–4311 (2011). https://doi.org/10.1021/jm200371q

    Article  Google Scholar 

  70. Matsoukas, M.T., Potamitis, C., Plotas, P., Androutsou, M.E., Agelis, G., Matsoukas, J., Zoumpoulakis, P.: Insights into AT1 receptor activation through AngII binding studies. J. Chem. Inf. Model. 53(11), 2798–2811 (2013). https://doi.org/10.1021/ci4003014

    Article  Google Scholar 

  71. Oates, J., Watts, A.: Uncovering the intimate relationship between lipids, cholesterol and GPCR activation. Curr. Opin. Struct. Biol. 21(6), 802–807 (2011). https://doi.org/10.1016/j.sbi.2011.09.007

    Article  Google Scholar 

  72. Sengupta, D., Chattopadhyay, A.: Identification of cholesterol binding sites in the Serotonin1A receptor. J. Phys. Chem. B 116(43), 12991–12996 (2012). https://doi.org/10.1021/jp309888u

    Article  Google Scholar 

  73. Khelashvili, G., Grossfield, A., Feller, S.E., Pitman, M.C., Weinstein, H.: Structural and dynamic effects of cholesterol at preferred sites of interaction with rhodopsin identified from microsecond length molecular dynamics simulations. Proteins 76(2), 403–417 (2009). https://doi.org/10.1002/prot.22355

    Article  Google Scholar 

  74. Fillion, D., Cabana, J., Guillemette, G., Leduc, R., Lavigne, P., Escher, E.: Structure of the human angiotensin II Type 1 (AT(1)) receptor bound to angiotensin II from multiple chemoselective photoprobe contacts reveals a unique peptide binding mode. J. Biol. Chem. 288(12), 8187–8197 (2013). https://doi.org/10.1074/jbc.M112.442053

    Article  Google Scholar 

  75. Unal, H., Jagannathan, R., Bhatnagar, A., Tirupula, K., Desnoyer, R., Karnik, S.S.: Long range effect of mutations on specific conformational changes in the extracellular loop 2 of angiotensin II type 1 receptor. J. Biol. Chem. 288(1), 540–551 (2013). https://doi.org/10.1074/jbc.M112.392514

    Article  Google Scholar 

  76. Vauquelin, G., Packeu, A.: Ligands, their receptors and … plasma membranes. Mol. Cell Endocrinol. 311(1–2), 1–10 (2009). https://doi.org/10.1016/j.mce.2009.07.022

    Article  Google Scholar 

  77. Seddon, A.M., Casey, D., Law, R.V., Gee, A., Templer, R.H., Ces, O.: Drug interactions with lipid membranes. Chem. Soc. Rev. 38(9), 2509–2519 (2009). https://doi.org/10.1039/b813853m

    Article  Google Scholar 

  78. Matsoukas, M.T., Cordomi, A., Rios, S., Pardo, L., Tselios, T.: Ligand binding determinants for angiotensin II type 1 receptor from computer simulations. J. Chem. Inf. Model. 53(11), 2874–2883 (2013). https://doi.org/10.1021/ci400400m

    Article  Google Scholar 

  79. Hodzic, A., Zoumpoulakis, P., Pabst, G., Mavromoustakos, T., Rappolt, M.: Losartan’s affinity to fluid bilayers modulates lipid-cholesterol interactions. Phys. Chem. Chem. Phys. 14(14), 4780–4788 (2012). https://doi.org/10.1039/c2cp40134g

    Article  Google Scholar 

  80. de Meyer, F.J.M., Benjamini, A., Rodgers, J.M., Misteli, Y., Smit, B.: Molecular simulation of the DMPC-cholesterol phase diagram. J. Phys. Chem. B 114(32), 10451–10461 (2010). https://doi.org/10.1021/jp103903s

    Article  Google Scholar 

  81. Bennett, W.F.D., Tieleman, D.P.: Computer simulations of lipid membrane domains. Biochim. Biophys. Acta 1828(8), 1765–1776 (2013). https://doi.org/10.1016/j.bbamem.2013.03.004

    Article  Google Scholar 

  82. Corvera, E., Mouritsen, O.G., Singer, M.A., Zuckermann, M.J.: The permeability and the effect of acyl-chain length for phospholipid bilayers containing cholesterol: theory and experiment. Biochim. Biophys. Acta 1107(2), 261–270 (1992)

    Article  Google Scholar 

  83. Haines, T.H.: Do sterols reduce proton and sodium leaks through lipid bilayers? Prog. Lipid Res. 40(4), 299–324 (2001)

    Article  Google Scholar 

  84. Grossfield, A.: Recent progress in the study of G protein-coupled receptors with molecular dynamics computer simulations. Biochim. Biophys. Acta 1808(7), 1868–1878 (2011). https://doi.org/10.1016/j.bbamem.2011.03.010

    Article  Google Scholar 

  85. Kellici, T.F., Liapakis, G., Tzakos, A.G., Mavromoustakos, T.: Pharmaceutical compositions for antihypertensive treatments: a patent review. Expert Opin. Ther. Pat. 25(11), 1305–1317 (2015). https://doi.org/10.1517/13543776.2015.1086337

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by CERIC funded programme (proposal number 20152002), for the promotion of the exchange and scientific cooperation between Greece and Germany IKYDA 2015 and by the Cy-Tera Project (ΝΕΑ ΥΠΟΔΟΜΗ/ΣΤΡΑΤΗ/0308/31), which is co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research Promotion Foundation.

Author information

Authors and Affiliations

  1. Department of Chemistry, National and Kapodistrian University of Athens, 15771, Panepistimiopolis Zografou, Greece

    Dimitrios Ntountaniotis, Tahsin F. Kellici & Thomas Mavromoustakos

  2. Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece

    Tahsin F. Kellici

  3. Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, 11527, Athens, Greece

    Paraskevi Gkeka, Zoe Cournia & Ioannis Galdadas

  4. Sanofi Aventis Group, Paris, France

    Paraskevi Gkeka

  5. Department of Inorganic Chemistry and Technology, National Institute of Chemistry, Hajdrihova 19, 1001, Ljubljana, Slovenia

    Gregor Mali

  6. Institute of Biophysical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany

    Johanna Becker-Baldus & Clemens Glaubitz

  7. Institute of Inorganic Chemistry, Graz University of Technology, Graz, Austria

    Manfred Kriechbaum

  8. School of Food Science & Nutrition, University of Leeds, Woodhouse Ln, Leeds, LS2 9JT, UK

    Michael Rappolt

  9. Department of Pharmacology, School of Medicine, University of Crete, 71003, Heraklion, Crete, Greece

    George Liapakis

Authors
  1. Dimitrios Ntountaniotis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tahsin F. Kellici
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paraskevi Gkeka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zoe Cournia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ioannis Galdadas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gregor Mali
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Johanna Becker-Baldus
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Clemens Glaubitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Manfred Kriechbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael Rappolt
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. George Liapakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Thomas Mavromoustakos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Mavromoustakos .

Editor information

Editors and Affiliations

  1. School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece

    Costas Demetzos

  2. School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece

    Natassa Pippa

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ntountaniotis, D. et al. (2019). Drug-Membrane Interactions in the Renin Angiotensin System. In: Demetzos, C., Pippa, N. (eds) Thermodynamics and Biophysics of Biomedical Nanosystems. Series in BioEngineering. Springer, Singapore. https://doi.org/10.1007/978-981-13-0989-2_10

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-0989-2_10

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-0988-5

  • Online ISBN: 978-981-13-0989-2

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation