Drug Discovery
  Molecular Analysis
  Organic and Organometallic Chemistry
  Medicinal Chemistry
  Structural Biology & Chemistry
  > Funded projects
  > Collaborations
  > Publications
  Molecular Endocrinology
  Signal Mediated Gene Expression
  Molecular & Cellular Ageing
  Biomedical Applications
  Holistic Approaches in Health
  Chemical Carcinogenesis and Genetic Toxicology
  Metabolic Engineering-Bioinformatics
  Enzyme and Synthetic Biotechnology
  Biomimetics & Nanobiotechnology

Structural Biology & Chemistry



Tsitsanou KE, Drakou CE, Thireou T, Gruber AV, Kythreoti G, Azem A, Fessas D, Eliopoulos E, Iatrou K & Zographos SE (2013) Crystal and Solution Studies of the "Plus-C" Odorant-binding Protein 48 from Anopheles gambiae CONTROL OF BINDING SPECIFICITY THROUGH THREE-DIMENSIONAL DOMAIN SWAPPING. Journal of Biological Chemistry 288, 33427-33438.

Tsitsanou KE, Hayes JM, Keramioti M, Mamais M, Oikonomakos NG, Kato A, Leonidas DD & Zographos SE (2013) Sourcing the affinity of flavonoids for the glycogen phosphorylase inhibitor site via crystallography, kinetics and QM/MM-PBSA binding studies: Comparison of chrysin and flavopiridol. Food Chem Toxicol 61, 14-27.

Skamnaki VT, Peumans WJ, Kantsadi AL, Cubeta MA, Plas K, Pakala S, Zographos SE, Smagghe G, Nierman WC, Van Damme EJM & Leonidas DD (2013) Structural analysis of the Rhizoctoniasolani agglutinin reveals a domain-swapping dimeric assembly. Febs Journal 280, 1750-1763.

Louros NN, Iconomidou VA, Tsiolaki PL, Chrysina ED, Baltatzis GE, Patsouris ES & Hamodrakas SJ (2013) An N-terminal pro-atrial natriuretic peptide (NT-proANP) 'aggregation-prone' segment involved in isolated atrial amyloidosis. FEBS Lett 588, 52-57.

Charavgi MD, Dimarogona M, Topakas E, Christakopoulos P & Chrysina ED (2013) The structure of a novel glucuronoyl esterase from Myceliophthora thermophila gives new insights into its role as a potential biocatalyst. Acta Crystallographica Section D-Biological Crystallography 69, 63-73.



Tsitsanou KE, Thireou T, Drakou CE, Koussis K, Keramioti MV, Leonidas DD, Eliopoulos E, Iatrou K & Zographos SE (2012) Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents. Cellular and Molecular Life Sciences 69, 283-297.

Parmenopoulou V, Chatzileontiadou DSM, Manta S, Bougiatioti S, Maragozidis P, Gkaragkouni DN, Kaffesaki E, Kantsadi AL, Skamnaki VT, Zographos SE, Zounpoulakis P, Balatsos NAA, Komiotis D & Leonidas DD (2012) Triazole pyrimidine nucleosides as inhibitors of Ribonuclease A. Synthesis, biochemical, and structural evaluation. Bioorganic & Medicinal Chemistry 20, 7184-7193.

Nagy V, Felfoldi N, Konya B, Praly JP, Docsa T, Gergely P, Chrysina ED, Tiraidis C, Kosmopoulou MN, Alexacou KM, Konstantakaki M, Leonidas DD, Zographos SE, Oikonomakos NG, Kozmon S, Tvaroska I & Somsak L (2012) N-(4-Substituted-benzoyl)-N '-(beta-D-glucopyranosyl)ureas as inhibitors of glycogen phosphorylase: Synthesis and evaluation by kinetic, crystallographic, and molecular modelling methods. Bioorganic & Medicinal Chemistry 20, 1801-1816.

Manta S, Xipnitou A, Kiritsis C, Kantsadi AL, Hayes JM, Skamnaki VT, Lamprakis C, Kontou M, Zoumpoulakis P, Zographos SE, Leonidas DD & Komiotis D (2012) 3 '-Axial CH2OH Substitution on Glucopyranose does not Increase Glycogen Phosphorylase Inhibitory Potency. QM/MM-PBSA Calculations Suggest Why. Chemical Biology & Drug Design 79, 663-673.

Kantsadi AL, Manta S, Psarra AMG, Dimopoulou A, Kiritsis C, Parmenopoulou V, Skamnaki VT, Zoumpoulakis P, Zographos SE, Leonidas DD & Komiotis D (2012) The binding of C5-alkynyl and alkylfurano[2,3-d]pyrimidine glucopyranonucleosides to glycogen phosphorylase b: Synthesis, biochemical and biological assessment. European Journal of Medicinal Chemistry 54, 740-749.

Kantsadi AL, Hayes JM, Manta S, Skamnaki VT, Kiritsis C, Psarra AMG, Koutsogiannis Z, Dimopoulou A, Theofanous S, Nikoleousakos N, Zoumpoulakis P, Kontou M, Papadopoulos G, Zographos SE, Komiotis D & Leonidas DD (2012) The s-Hole Phenomenon of Halogen Atoms Forms the Structural Basis of the Strong Inhibitory Potency of C5 Halogen Substituted Glucopyranosyl Nucleosides towards Glycogen Phosphorylase b. Chemmedchem 7, 722-732.

Goyard D, Baron M, Skourti PV, Chajistamatiou AS, Docsa T, Gergely P, Chrysina ED, Praly JP & Vidal S (2012) Synthesis of 1,2,3-triazoles from xylosyl and 5-thioxylosyl azides: evaluation of the xylose scaffold for the design of potential glycogen phosphorylase inhibitors. Carbohydrate Research 364, 28-40.

Feuillastre S, Chajistamatiou AS, Potamitis C, Zervou M, Zoumpoulakis P, Chrysina ED, Praly JP & Vidal S (2012) C-Glucosylated malonitrile as a key intermediate towards carbohydrate-based glycogen phosphorylase inhibitors. Bioorganic & Medicinal Chemistry 20, 5592-5599.

Drakou CE, Malekkou A, Hayes JM, Lederer CW, Leonidas DD, Oikonomakos NG, Lamond AI, Santama N & Zographos SE (2012) hCINAP is an atypical mammalian nuclear adenylate kinase with an ATPase motif: Structural and functional studies. Proteins-Structure Function and Bioinformatics 80, 206-220.

Dimarogona M, Topakas E, Christakopoulos P & Chrysina ED (2012) The structure of a GH10 xylanase from Fusarium oxysporum reveals the presence of an extended loop on top of the catalytic cleft. Acta Crystallographica Section D-Biological Crystallography 68, 735-742.



Kun S, Nagy GZ, Toth M, Czecze L, Albert NVN, Docsa T, Gergely P, Charavgi MD, Skourti PV, Chrysina ED, Patonay T & Somsak L (2011) Synthesis of variously coupled conjugates of D-glucose, 1,3,4-oxadiazole, and 1,2,3-triazole for inhibition of glycogen phosphorylase. Carbohydrate Research 346, 1427-1438.

Hayes JM, Skamnaki VT, Archontis G, Lamprakis C, Sarrou J, Bischler N, Skaltsounis AL, Zographos SE & Oikonomakos NG (2011) Kinetics, in silico docking, molecular dynamics, and MM-GBSA binding studies on prototype indirubins, KT5720, and staurosporine as phosphorylase kinase ATP-binding site inhibitors: The role of water molecules examined. Proteins-Structure Function and Bioinformatics 79, 703-719.

Alexacou KM, Zhang YZ, Praly JP, Zographos SE, Chrysina ED, Oikonomakos NG & Leonidas DD (2011) Halogen-substituted (C-beta-D-glucopyranosyl)-hydroquinone regioisomers: Synthesis, enzymatic evaluation and their binding to glycogen phosphorylase. Bioorganic & Medicinal Chemistry 19, 5125-5136.



Tsirkone VG, Tsoukala E, Lamprakis C, Manta S, Hayes JM, Skamnaki VT, Drakou C, Zographos SE, Komiotis D & Leonidas DD (2010) 1-(3-Deoxy-3-fluoro-beta-D-glucopyranosyl) pyrimidine derivatives as inhibitors of glycogen phosphorylase b: Kinetic, crystallographic and modelling studies. Bioorganic & Medicinal Chemistry 18, 3413-3425.

Felfoldi N, Toth M, Chrysina ED, Charavgi MD, Alexacou KM & Somsak L (2010) Synthesis of new glycosyl biuret and urea derivatives as potential glycoenzyme inhibitors. Carbohydrate Research 345, 208-213.

Alexacou KM, Tenchiu AC, Chrysina ED, Charavgi MD, Kostas ID, Zographos SE, Oikonomakos NG & Leonidas DD (2010) The binding of beta-D-glucopyranosyl-thiosemicarbazone derivatives to glycogen phosphorylase: A new class of inhibitors. Bioorganic & Medicinal Chemistry 18, 7911-7922.



Venien-Bryan C, Jonic S, Skamnaki V, Brown N, Bischler N, Oikonomakos NG, Boisset N & Johnson LN (2009) The Structure of Phosphorylase Kinase Holoenzyme at 9.9 angstrom Resolution and Location of the Catalytic Subunit and the Substrate Glycogen Phosphorylase. Structure 17, 117-127.

Tsirkone VG, Dossi K, Drakou C, Zographos SE, Kontou M & Leonidas DD (2009) Inhibitor design for ribonuclease A: the binding of two 5 '-phosphate uridine analogues. Acta Crystallographica Section F-Structural Biology and Crystallization Communications 65, 671-677.

Samanta A, Leonidas DD, Dasgupta S, Pathak T, Zographos SE & Oikonomakos NG (2009) Morpholino, Piperidino, and Pyrrolidino Derivatives of Pyrimidine Nucleosides as Inhibitors of Ribonuclease A: Synthesis, Biochemical, and Crystallographic Evaluation. Journal of Medicinal Chemistry 52, 932-942.

Chrysina ED, Bokor E, Alexacou KM, Charavgi MD, Oikonomakos GN, Zographos SE, Leonidas DD, Oikonomakos NG & Laszlo S (2009) Amide-1,2,3-triazole bioisosterism: the glycogen phosphorylase case. Tetrahedron-Asymmetry 20, 733-740.

Benltifa M, Hayes JM, Vidal S, Gueyrard D, Goekjian PG, Praly JP, Kizilis G, Tiraidis C, Alexacou KM, Chrysina ED, Zographos SE, Leonidas DD, Archontis G & Oikonomakos NG (2009) Glucose-based spiro-isoxazolines: A new family of potent glycogen phosphorylase inhibitors. Bioorganic & Medicinal Chemistry 17, 7368-7380.

Dossi K, Tsirkone VG, Hayes JM, Matousek J, Pouckova P, Soucek J, Zadinova M, Zographos SE & Leonidas DD (2009) Mapping the ribonucleolytic active site of bovine seminal ribonuclease. The binding of pyrimidinyl phosphonucleotide inhibitors. European Journal of Medicinal Chemistry 44, 4496-4508.



Wen XA, Sun HB, Liu J, Cheng KG, Zhang P, Zhang LY, Hao J, Ni PZ, Zographos SE, Leonidas DD, Alexacou KM, Gimisis T, Hayes JM & Oikonomakos NG (2008) Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: Synthesis, structure-activity relationships, and X-ray crystallographic studies. Journal of Medicinal Chemistry 51, 3540-3554.

Sathisha GJ, Prakash YKS, Chachadi VB, Nagaraja NN, Inamdar SR, Leonidas DD, Savithri HS & Swamy BM (2008) X-ray sequence ambiguities of Sclerotium rolfsii lectin resolved by mass spectrometry. Amino Acids 35, 309-320.

Li HQ, Liu T, Zhang YM, Favre S, Bello C, Vogel P, Butters TD, Oikonomakos NG, Marrot J & Bleriot Y (2008) New synthetic seven-membered 1-azasugars displaying potent inhibition towards glycosidases and glucosylceramide transferase. Chembiochem 9, 253-260.

Alexacou KM, Hayes JM, Tiraidis C, Zographos SE, Leonidas DD, Chrysina ED, Archontis G, Oikonomakos NG, Paul JV, Varghese B & Loganathan D (2008) Crystallographic and computational studies on 4-phenyl-N-(beta-D-glucopyranosyl)-1H-1,2, 3-triazole-1-acetamide, an inhibitor of glycogen phosphorylase: Comparison with alpha-D-glucose, N-acetyl-beta-D-glucopyranosylamine and N-benzoyl-N '-beta-D-glucopyranosyl urea binding. Proteins-Structure Function and Bioinformatics 71, 1307-1323.



Tiraidis C, Alexacou KM, Zographos SE, Leonidas DD, Gimisis T & Oikonomakos NG (2007) FR258900, a potential anti-hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase. Protein Science 16, 1773-1782.

Polydoridis S, Leonidas DD, Oikonomakos NG & Archontis G (2007) Recognition of ribonuclease a by 3 '-5 '-pyrophosphate-linked dinucleotide inhibitors: A molecular dynamics/continuum electrostatics analysis. Biophysical Journal 92, 1659-1672.

Pantelidou M, Zographos SE, Lederer CW, Kyriakides T, Pfaffl MW & Santama N (2007) Differential expression of molecular motors in the motor cortex of sporadic ALS. Neurobiology of Disease 26, 577-589.

Leonidas DD, Swamy BM, Hatzopoulos GN, Gonchigar SJ, Chachadi VB, Inamdar SR, Zographos SE & Oikonomakos NG (2007) Structural basis for the carbohydrate recognition of the Sclerotium rolfsii lectin. Journal of Molecular Biology 368, 1145-1161.

He L, Zhang YZ, Tanoh M, Chen GR, Praly JP, Chrysina ED, Tiraidis C, Kosmopoulou M, Leonidas DD & Oikonomakos NG (2007) In the search of glycogen phosphorylase inhibitors: 4. Synthesis of C-D-glycopyranosylbenzo(hydro)quinones - Inhibition of and binding to glycogen phosphorylase in the crystal. European Journal of Organic Chemistry, 596-606.

Birch AM, Kenny PW, Oikonomakos NG, Otterbein L, Schofield P, Whittamore PRO & Whalley DP (2007) Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors. Bioorganic & Medicinal Chemistry Letters 17, 394-399.



Whittamore PRO, Addie MS, Bennett SNL, Birch AM, Butters M, Godfrey L, Kenny PW, Morley AD, Murray PM, Oikonomakos NG, Otterbein LR, Pannifer AD, Parker JS, Readman K, Siedlecki PS, Schofield P, Stocker A, Taylor MJ, Townsend LA, Whalley DP & Whitehouse J (2006) Novel thienopyrrole glycogen phosphorylase inhibitors: Synthesis, in vitro SAR and crystallographic studies. Bioorganic & Medicinal Chemistry Letters 16, 5567-5571.

Petsalakis EI, Chrysina ED, Tiraidis C, Hadjiloi T, Leonidas DD, Oikonomakos NG, Aich U, Varghese B & Loganathan D (2006) Crystallographic studies on N-azidoacetyl-beta-D-glucopyranosylamine, an inhibitor of glycogen phosphorylase: Comparison with N-acetyl-beta-D-glucopyranosylamine. Bioorganic & Medicinal Chemistry 14, 5316-5324.

Oikonomakos NG, Tiraidis C, Leonidas DD, Zographos SE, Kristiansen M, Jessen CU, Norskov-Lauritsen L & Agius L (2006) Iminosugars as potential inhibitors of glycogenolysis: Structural insights into the molecular basis of glycogen phosphorylase inhibition. Journal of Medicinal Chemistry 49, 5687-5701.

Lukacs CM, Oikonomakos NG, Crowther RL, Hong LN, Kammlott RU, Levin W, Li S, Liu CM, Lucas-McGady D, Pietranico S & Reik L (2006) The crystal structure of human muscle glycogen phosphorylase a with bound glucose and AMP: An intermediate conformation with T-State and R-State features. Proteins-Structure Function and Bioinformatics 63, 1123-1126.

Leonidas DD, Maiti TK, Samanta A, Dasgupta S, Pathak T, Zographos SE & Oikonomakos NG (2006) The binding of 3 '-N-piperidine-4-carboxyl-3 '-deoxy-ara-uridine to ribonuclease A in the crystal. Bioorganic & Medicinal Chemistry 14, 6055-6064.

Hampson LJ, Arden C, Agius L, Ganotidis M, Kosmopoulou MN, Tiraidis C, Elemes Y, Sakarellos C, Leonidas DD & Oikonomakos NG (2006) Bioactivity of glycogen phosphorylase inhibitors that bind to the purine nucleoside site. Bioorganic & Medicinal Chemistry 14, 7835-7845.

Hadjiloi T, Tiraidis C, Chrysina ED, Leonidas DD, Oikonomako NG, Tsipos P & Gimisis T (2006) Binding of oxalyl derivatives of beta-D-glucopyranosylamine to muscle glycogen phosphorylase b. Bioorganic & Medicinal Chemistry 14, 3872-3882.

Anagnostou E, Kosmopoulou MN, Chrysina ED, Leonidas DD, Hadjiloi T, Tiraidis C, Zographos SE, Gyorgydeak Z, Somsak L, Docsa T, Gergely P, Kolisis FN & Oikonomakos NG (2006) Crystallographic studies on two bioisosteric analogues, N-acetyl-beta-D-glucopyranosylamine and N-trifluoroacetyl-beta-D-glucopyranosylamine, potent inhibitors of muscle glycogen phosphorylase. Bioorganic & Medicinal Chemistry 14, 181-189.



Watson KA, Chrysina ED, Tsitsanou KE, Zographos SE, Archontis G, Fleet GWJ & Oikonomakos NG (2005) Kinetic and crystallographic studies of glucopyranose spirohydantoin and glucopyranosylamine analogs inhibitors of glycogen phosphorylase. Proteins-Structure Function and Bioinformatics 61, 966-983.

Oikonomakos NG, Kosmopoulou MN, Chrysina ED, Leonidas DD, Kostas ID, Wendt KU, Klabunde T & Defossa E (2005) Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs. Protein Science 14, 1760-1771.

Kosmopoulou MN, Leonidas DD, Chrysina ED, Eisenbrand G & Oikonomakos NG (2005) Indirubin-3 '-aminooxy-acetate inhibits glycogen phosphorylase by binding at the inhibitor and the allosteric site. Broad specificities of the two sites. Letters in Drug Design & Discovery 2, 377-390.

Klabunde T, Wendt KU, Kadereit D, Brachvogel V, Burger HJ, Herling AW, Oikonomakos NG, Kosmopoulou MN, Schmoll D, Sarubbi E, von Roedern E, Schonafinger K & Defossa E (2005) Acyl ureas as human liver glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Journal of Medicinal Chemistry 48, 6178-6193.

Hatzopoulos GN, Leonidas DD, Kardakaris R, Kobe J & Oikonomakos NG (2005) The binding of IMP to ribonuclease A. Febs Journal 272, 3988-4001.

Chrysina ED, Kosmopoulou MN, Tiraidis C, Kardakaris R, Bischler N, Leonidas DD, Hadady Z, Somsak L, Docsa T, Gergely P & Oikonomakos NG (2005) Kinetic and crystallographic studies on 2-(beta-D-glucopyranosyl)-5-methyl-1,3,4-oxadiazole, -benzothiazole, and -benzimidazole, inhibitors of muscle glycogen phosphorylase b. Evidence for a new binding site. Protein Science 14, 873-888.

Chrysina ED, Kosmopoulou MN, Kardakaris R, Bischler N, Leonidas DD, Kannan T, Loganathan D & Oikonomakos NG (2005) Binding of beta-D-glucopyranosyl bismethoxyphosphoramidate to glycogen phosphorylase b: kinetic and crystallographic studies. Bioorganic & Medicinal Chemistry 13, 765-772.

Archontis G, Watson KA, Xie Q, Andreou G, Chrysina ED, Zographos SE, Oikonomakos NG & Karplus M (2005) Glycogen phosphorylase inhibitors: A free energy perturbation analysis of glucopyranose spirohydantoin analogues. Proteins-Structure Function and Bioinformatics 61, 984-998.



Chrysina ED, Chajistamatiou A & Chegkazi M (2011) From Structure-Based to Knowledge-Based Drug Design Through X-Ray Protein Crystallography: Sketching Glycogen Phosphorylase Binding Sites. Current Medicinal Chemistry 18, 2620-2629.

Hayes JM & Leonidas DD (2010) Computation as a Tool for Glycogen Phosphorylase Inhibitor Design. Mini-Reviews in Medicinal Chemistry 10, 1156-1174.

Chrysina ED (2010) The Prototype of Glycogen Phosphorylase. Mini-Reviews in Medicinal Chemistry 10, 1093-1101.

Somsak L, Czifrak K, Toth M, Bokor E, Chrysina ED, Alexacou KM, Hayes JM, Tiraidis C, Lazoura E, Leonidas DD, Zographos SE & Oikonomakos NG (2008) New Inhibitors of Glycogen Phosphorylase as Potential Antidiabetic Agents. Current Medicinal Chemistry 15, 2933-2983.

Oikonomakos NG & Somsak L (2008) Advances in glycogen phosphorylase inhibitor design. Current Opinion in Investigational Drugs 9, 379-395.


Book Chapters

Joseph M. Hayes and Georgios Archontis (2012). MM-GB(PB)SA Calculations of Protein-Ligand Binding Free Energies. In Molecular Dynamics - Studies of Synthetic and Biological Macromolecules (Prof. Lichang Wang Ed.), ISBN: 978-953-51-0444-5, InTech, DOI: 10.5772/37107. Available from:

N.G. Oikonomakos, E.D. Chrysina, C. Tiraidis, D.D. Leonidas, S.E. Zographos (2007). Conformation flexibility of the 280s peptide loop in glycogen phosphorylase: implications for inhibitor design. In 5th Hellenic Forum on Bioactive Peptides (Cordopatis, P., Manessi-Zoupa, E.; Pairas, G. N.; eds.), Typorama, Patras, Vol.5, pp. 283-289. ISBN: 960-7620-32-1

N.G. Oikonomakos, M. N. Kosmopoulou, D. D. Leonidas, E. D. Chrysina, C. Tiraidis, N. Bischler, K. E. Tsitsanou, S. E. Zographos, I. D. Kostas, and G. Eisenbrand (2006). Indirubin and indigo analogues as potential inhibitors of glycogenolysis: structural basis of glycogen phosphorylase inhibition. In Indirubin, the red shade of indigo (Meijer L., Guyard N., Skaltsounis L. & Eisenbrand G., eds) Editions “Life in Progress”, Station Biologique, Roscoff, Chapter 18, pp. 177-189. ISBN: 2-9518029-0-0













National Hellenic Research Foundation (NHRF), 48 Vassileos Constantinou Ave., 11635 Athens, Greece, Tel. +302107273700, Fax. +302107246618