Homepage » Research » Molecular Structure Analysis of biologically active molecules using Molecular Calculations and NMR spectroscopy

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  • Interactions monitored by NMR Spectroscopy and Molecular Modeling

  • Peptides and Natural products structural studies using 2D NMR spectroscopy and Molecular Modeling

  • Structure Based Drug Design, In Silico screening

The conformational behavior of different peptides, natural products as well as small synthetic molecules is assessed using NMR spectroscopic data (NOEs and  3J coupling constants) in combination with computational molecular modeling. Calculation of the NOESY peak intensities is performed by using the complete relaxation matrix analysis (CORMA), while structures generated by a Monte Carlo conformational search were considered for the best match of the NMR data. Relative populations of the different conformers is extracted using the NAMFIS approach.

The interactions of the 28 amino acid residue N-terminal fragment of the β-amyloid peptide (β-AP) of Alzheimer’s disease, [β-AP(1-28)], with small molecules has been studied through the observation of transferred NOEs and may provide a means of screening for the identification of possible inhibitors of the formation of neurotoxic β-AP assemblies.

Selected Publications

Krypotou, E., Kosti, V., Amillis, S., Myrianthopoulos, V., Mikros, E., Diallinas, G. Modeling, substrate docking, and mutational analysis identify residues essential for the function and specificity of a eukaryotic purine-cytosine NCS1 transporter (2012) Journal of Biological Chemistry, 287 (44), pp. 36792-36803.
DOI: 10.1074/jbc.M112.400382

Vontzalidou, A., Zoidis, G., Chaita, E., Makropoulou, M., Aligiannis, N., Lambrinidis, G., Mikros, E., Skaltsounis, A.-L. Design, synthesis and molecular simulation studies of dihydrostilbene derivatives as potent tyrosinase inhibitors (2012) Bioorganic and Medicinal Chemistry Letters, 22 (17), pp. 5523-5526.
DOI: 10.1016/j.bmcl.2012.07.029

Kosti, V., Lambrinidis, G., Myrianthopoulos, V., Diallinas, G., Mikros, E. Identification of the substrate recognition and transport pathway in a eukaryotic member of the nucleobase-ascorbate transporter (NAT) family (2012) PLoS ONE, 7 (7), art. no. e41939, .
DOI: 10.1371/journal.pone.0041939

Amillis, S., Kosti, V., Pantazopoulou, A., Mikros, E., Diallinas, G. Mutational analysis and modeling reveal functionally critical residues in transmembrane segments 1 and 3 of the UapA transporter (2011) Journal of Molecular Biology, 411 (3), pp. 567-580.
DOI: 10.1016/j.jmb.2011.06.024

Soares-Silva, I., Sá-Pessoa, J., Myrianthopoulos, V., Mikros, E., Casal, M., Diallinas, G. A substrate translocation trajectory in a cytoplasm-facing topological model of the monocarboxylate/H + symporter Jen1p (2011) Molecular Microbiology, 81 (3), pp. 805-817.
DOI: 10.1111/j.1365-2958.2011.07729.x

Tite, T., Lougiakis, N., Myrianthopoulos, V., Marakos, P., Mikros, E., Pouli, N., Tenta, R., Fragopoulou, E., Nomikos, T. Design and synthesis of new C-nucleosides as potential adenosine deaminase inhibitors (2010) Tetrahedron, 66 (50), pp. 9620-9628.
DOI: 10.1016/j.tet.2010.10.005

Benaki, D., Stathopoulou, K., Leondiadis, L., Ferderigos, N., Pelecanoua, M., Mikros, E. Detection of interactions of the β-amyloid peptide with small molecules employing transferred NOEs (2009) Journal of Peptide Science, 15 (6), pp. 435-441.
DOI: 10.1002/psc.1138

Zoidis, G., Benaki, D., Myrianthopoulos, V., Naesens, L., Clercq, E.D., Mikros, E., Kolocouris, N. Synthesis of 1,2-annulated adamantane heterocycles: structural determination studies of a bioactive cyclic sulfite (2009) Tetrahedron Letters, 50 (22), pp. 2671-2675.
DOI: 10.1016/j.tetlet.2009.03.132

Kourafalos, V.N., Tite, T., Mikros, E., Marakos, P., Pouli, N., Balzarini, J. The synthesis of a novel C-nucleoside designed as guanosine analogue (2008) Synlett, (20), pp. 3129-3132. h
DOI: 10.1055/s-0028-1087276

Fragaki, G., Stefanaki, I., Dais, P., Mikros, E. Conformational properties of the macrocyclic trichothecene mycotoxin verrucarin A in solution (2008) Magnetic Resonance in Chemistry, 46 (12), pp. 1102-1111.
DOI: 10.1002/mrc.2298

Stanica, R.M., Benaki, D., Rodis, F.I., Mikros, E., Tsoukatos, D., Tselepis, A., Tsikaris, V. Structure-activity relationships of αIIb 313-320 derived peptide inhibitors of human platelet aggregation (2008) Journal of Peptide Science, 14 (11), pp. 1195-1202.
DOI: 10.1002/psc.1060

Tsikouris, O., Bartl, T., Toušek, J., Lougiakis, N., Tite, T., Marakos, P., Pouli, N., Mikros, E., Marek, R. NMR study of 5-substituted pyrazolo[3,4-c]pyridine derivatives (2008) Magnetic Resonance in Chemistry, 46 (7), pp. 643-649.
DOI: 10.1002/mrc.2226

Kourafalos, V.N., Marakos, P., Mikros, E., Pouli, N., Marek, J., Marek, R. Synthesis and tautomerism study of 7-substituted pyrazolo[3,4-c]pyridines (2006) Tetrahedron, 62 (51), pp. 11987-11993.
DOI: 10.1016/j.tet.2006.09.081

Benaki, D., Zikos, C., Evangelou, A., Livaniou, E., Vlassi, M., Mikros, E.,Pelecanou, M. Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal cell death in Alzheimer’s disease (2006) Biochemical and Biophysical Research Communications, 349 (2), pp. 634-642.
DOI: 10.1016/j.bbrc.2006.08.087

Hadjipavlou, C., Kostakis, I.K., Pouli, N., Marakos, P., Mikros, E. 1-Ethyl-1H-3-nitrobenzopyrano[4,3,2-cd]isoindole: a novel heterocyclic ring system bearing an unusually labile deuterium-exchangeable aromatic proton (2006) Tetrahedron Letters, 47 (22), pp. 3681-3684.
DOI: 10.1016/j.tetlet.2006.03.130

Dais, P., Stefanaki, I., Fragaki, G., Mikros, E. Conformational analysis of ochratoxin A by NMR spectroscopy and computational molecular modeling (2005) Journal of Physical Chemistry B, 109 (35), pp. 16926-16936.
DOI: 10.1021/jp058035e

Benaki, D., Zikos, C., Evangelou, A., Livaniou, E., Vlassi, M., Mikros, E., Pelecanou, M. Solution structure of humanin, a peptide against Alzheimer’s disease-related neurotoxicity (2005) Biochemical and Biophysical Research Communications, 329 (1), pp. 152-160.
DOI: 10.1016/j.bbrc.2005.01.100

Costopoulos, B., Benaki, D., Pelecanou, M., Mikros, E., Stassinopoulou, C.I., Varvarigou, A.D., Archimandritis, S.C. Structural study by NMR of an oxorhenium-RGD decapeptide complex for application in radiotherapy (2004) Inorganic Chemistry, 43 (18), pp. 5598-5602.
DOI: 10.1021/ic049519c

Benaki, D.C., Mikros, E., Hamodrakas, S.J. Conformational analysis of peptide analogues of silkmoth chorion protein segments using CD, NMR and molecular modelling (2004) Journal of Peptide Science, 10 (6), pp. 381-392.
DOI: 10.1002/psc.540

Manios, T., Maniadakis, K., Kalogeraki, M., Mari, E., Terzakis, S., Magiatis, P., Mikros, E., Agalias, A., Spanos, I., Manios, V. Cocomposting olive residuals and green waste on Crete (2004) BioCycle, 45 (2), pp. 67-70.

Markidis, T., Mikros, E., Kokotos, G. Stereoselective intramolecular azide 1,3-dipolar cycloaddition (2003) Heterocycles, 60 (12), pp. 2637-2644.

Mikros, E., Labrinidis, G., Pérez, S. Conformational Analysis of C-Trehaloses Using Molecular Mechanics Calculations (2003) Journal of Carbohydrate Chemistry, 22 (6), pp. 407-421.
DOI: 10.1081/CAR-120025327

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 AT 1 receptor (2003) Chemistry and Physics of Lipids, 125 (1), pp. 13-25.
DOI: 10.1016/S0009-3084(03)00053-7

Panteleon, V., Marakos, P., Pouli, N., Mikros, E., Andreadou, I. Interactions of a series of novel spiropyranocoumarin derivatives with reactive oxygen species (2003) Journal of Pharmacy and Pharmacology, 55 (7), pp. 1029-1039.
DOI: 10.1211/0022357021512

Marakos, P., Pouli, N., Papakonstantinou-Garoufalias, S., Mikros, E. Structural characteristics of some mercaptoacetic acid hydrazides (2003) Journal of Molecular Structure, 650 (1-3), pp. 213-221.
DOI: 10.1016/S0022-2860(03)00158-3

Panteleon, V., Marakos, P., Pouli, N., Mikros, E., Andreadou, I. Synthesis, conformational analysis and free radical scavenging activity of some new spiropyranoquinolinones (2003) Chemical and Pharmaceutical Bulletin, 51 (5), pp. 522-529.

Biris, N., Stavrakoudis, A., Politou, A.S., Mikros, E., Sakarellos-Daitsiotis, M., Sakarellos, C., Tsikaris, V. The Ac-RGD-NH2 peptide as a probe of slow conformational exchange of short linear peptides in DMSO (2003) Biopolymers, 69 (1), pp. 72-86.
DOI: 10.1002/bip.10335

Benaki, D.C., Paxinou, E., Magafa, V., Pairas, G.N., Manessi-Zoupa, E., Cordopatis, P.A., Mikros, E. Conformational analysis of the nonapeptide leuprorelin using NMR and molecular modeling (2002) Letters in Peptide Science, 8 (2), pp. 77-87.
DOI: 10.1023/A:1015036903464

Benaki, D.C., Paxinou, E., Magafa, V., Pairas, G.N., Manessizoupa, E., Cordopatis, P.A., Mikros, E. Conformational analysis of the nonapeptide leuprorelin using NMR and molecular modeling (2001) International Journal of Peptide Research and Therapeutics, 8 (2), pp. 77-87.

Kostakis, I.K., Pouli, N., Marakos, P., Mikros, E., Skaltsounis, A.-L., Leonce, S., Atassi, G., Renard, P. Synthesis, cytotoxic activity, NMR study and stereochemical effects of some new pyrano[3,2-b]thioxanthen-6-ones and Pyrano[2,3-c]thioxanthen-7-ones (2001) Bioorganic and Medicinal Chemistry, 9 (11), pp. 2793-2802.
DOI: 10.1016/S0968-0896(01)00130-4

Mikros, E., Benaki, D., Humpfer, E., Spraul, M., Loukas, S., Stassinopoulou, C.I., Pelecanou, M. High-resolution NMR spectroscopy of the β-amyloid(1-28) fibril typical for Alzheimer’s disease (2001) Angewandte Chemie – International Edition, 40 (19), pp. 3603-3605.
DOI: 10.1002/1521-3773(20011001)40:19<3603::aid-anie3603>3.0.CO;2-5

Karali, A., Dais, P., Mikros, E., Heatley, F. Conformational analysis of poly(N-vinylcarbazole) by NMR spectroscopy and molecular modeling (2001) Macromolecules, 34 (16), pp. 5547-5554.
DOI: 10.1021/ma010117n

Mihopoulos, N., Vagias, C., Mikros, E., Scoullos, M., Roussis, V. Prevezols A and B: New brominated diterpenes from the red alga Laurencia obtusa (2001) Tetrahedron Letters, 42 (22), pp. 3749-3752.
DOI: 10.1016/S0040-4039(01)00538-X

Mikros, E., Labrinidis, G., Pérez, S. Conformational analysis of C-disaccharides using molecular mechanics calculations (2000) Journal of Carbohydrate Chemistry, 19 (9), pp. 1319-1349.

Fokialakis, N., Mitaku, S., Mikros, E., Skaltsounis, A.-L., Tillequin, F., Sevenet, T. Megistosarcimine and megistosarconine, two alkaloids from Sarcomelicope megistophylla (1999) Phytochemistry, 52 (8), pp. 1745-1748.
DOI: 10.1016/S0031-9422(99)00323-4

Mikros, E., Mitaku, S., Skaltsounis, A.-L., Libot, F., Tillequin, F., Koch, M. Stereochemical effects in some acronycine derivatives (1999) Magnetic Resonance in Chemistry, 37 (7), pp. 498-506.

Rinnbauer, M., Mikros, E., Peters, T. Conformational analysis of a complex between dolichos biflorus lectin and the forssman pentasaccharide using transferred noe build-up curves (1998) Journal of Carbohydrate Chemistry, 17 (2), pp. 217-230.

Kolocouris, A., Mikros, E., Kolocouris, N. Stereodynamics of ring and nitrogen inversion in spiroheterocycles. Conformational analysis of N-methylspiro[morpholine-3,2′-adamantane] and N-methylspiro[piperidine-2,2′-adamantane] using NMR spectroscopy and theoretical calculations (1998) Journal of the Chemical Society. Perkin Transactions 2, (7), pp. 1701-1708.

Mikros, E., Dais, P., Sauriol, F. Conformational analysis of asperlin by NMR spectroscopy and molecular modeling (1996) Carbohydrate Research, 294, pp. 1-13.
DOI: 10.1016/S0008-6215(96)00201-7

Imberty, A., Mollicone, R., Mikros, E., Carrupt, P.-A., Pérez, S., Oriol, R. How do antibodies and lectins recognize histo-blood group antigens? A 3D-QSAR study by comparative molecular field analysis (CoMFA) (1996) Bioorganic and Medicinal Chemistry, 4 (11), pp. 1979-1988.
DOI: 10.1016/S0968-0896(96)00179-4

Coutsolelos, A.G., Lux, D., Mikros, E. Synthesis and characterization of homo- and heteroporphyrin dimers involving a rhodium-indium bond (1996) Polyhedron, 15 (4), pp. 705-715.
DOI: 10.1016/0277-5387(95)00256-R

Imberty, A., Mikros, E., Koca, J., Mollicone, R., Oriol, R., Perez, S. Computer simulation of histo-blood group oligosaccharides: Energy maps of all constituting disaccharides and potential energy surfaces of 14 ABH and Lewis carbohydrate antigens (1995) Glycoconjugate Journal, 12 (3), pp. 331-349.
DOI: 10.1007/BF00731336

Davoras, E.M., Spyroulias, G.A., Mikros, E., Coutsolelos, A.G. 1H-NMR spectroscopic elucidation of stereochemical effects of substituted cerium porphyrin double-deckers (1994) Inorganic Chemistry, 33 (15), pp. 3430-3434.

Baudouin, G., Mitaku, S., Mikros, E., Skaltsounis, A.-L., Tillequin, F. Thermal dimerization of noracronycine (1992) Heterocycles, 34 (9), pp. 1691-1696.

Mikros, E., Gaudemer, F., Gaudemer, A. Structural studies of metalloporphyrins. 10. Complexes of water-soluble cobalt(III) porphyrins with amino acids: NMR Study of the conformation of the complexes with cobalt(III) tetrakis[4-(N-methylpyridiniumyl)]porphine (CoTMPyP) and cobalt(III) tetrakis(4-carboxylatophenyl)porphine (CoTCPP) (1991) Inorganic Chemistry, 30 (8), pp. 1806-1815.

Verchere-Beaur, C., Mikros, E., Perree-Fauvet, M., Gaudemer, A. Structural studies of metalloporphyrins. Part XI a: Complexes of water-soluble zinc(II) porphyrins with amino acids: Influence of ligand-ligand interactions on the stability of the complexes (1990) Journal of Inorganic Biochemistry, 40 (2), pp. 127-139.
DOI: 10.1016/0162-0134(90)80046-Z

Mikros, E., Gaudemer, A., Pasternack, R. Interactions of water-soluble zinc porphyrin with amino acids (1988) Inorganica Chimica Acta, 153 (4), pp. 199-200.