Ole Andersen

Ole Andreas Andersen joined the Diamond Industrial Liaison Office in 2025 as a Senior Industrial Liaison Scientist focusing on Macromolecular Crystallography, including the Diamond XChem fragment screening facility. Ole received his PhD from the University of Tromsø, Norway, in 2003. His work, supervised by Prof. Edward Hough, comprised crystallographic and biochemical studies aimed at elucidating the reaction mechanism of human phenylalanine hydroxylase. He held postdoctoral fellowships at the Norwegian Structural Biology Centre in Tromsø, under the supervision of Prof. Arne Smalås, and in the group of Daan van Aalten at the University of Dundee, where he worked on chitinases using protein crystallography as a tool for inhibitor design. Ole moved to industry in 2007 and worked 17 years in the Protein Sciences team at Evotec (UK) Ltd, Abingdon. His work focused on macromolecular crystallography, protein construct design, biophysical methods, and the structural characterisation of protein complexes with small-molecules, including fragments, covalent binders, peptides, peptidomimetics, RNA, DNA, as well as protein-protein complexes.

1.     Ryan, M. D., Parkes, A. L., Corbett, D., Dickie, A. P., Southey, M., Andersen, O. A., Stein, D. B., Barbeau, O. R., Sanzone, A., Thommes, P., Barker, J., Cain, R., Compper, C., Dejob, M., Dorali, A., Etheridge, D., Evans, S., Faulkner, A., Gadouleau, E., Gorman, T., Haase, D., Holbrow-Wilshaw, M., Krulle, T., Li, X., Lumley, C., Mertins, B., Napier, S., Odedra, R., Papadopoulos, K., Roumpelakis, V., Spear, K., Trimby, E., Williams, J., Zahn, M., Keefe, A. D., Zhang, Y., Soutter, H. T., Centrella, P. A., Clark, M. A., Cuozzo, J. W., Dumelin, C. E., Deng, B., Hunt, A., Sigel, E. A., Troast, D. M. & DeJonge, B. L. M. (2021) Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against Pseudomonas aeruginosa. J. Med. Chem. 64, 14377-14425.

2.     Zhang, J., Chan, A., Lippa, B., Cross, J. B., Liu, C., Yin, N., Romero, J. A., Lawrence, J., Heney, R., Herradura, P., Goss, J., Clark, C., Abel, C., Zhang, Y., Poutsiaka, K. M., Epie, F., Conrad, M., Mahamoon, A., Nguyen, K., Chavan, A., Clark, E., Li, T. C., Cheng, R. K., Wood, M., Andersen, O. A., Brooks, M., Kwong, J., Barker, J., Parr, I. B., Gu, Y., Ryan, M. D., Coleman, S. & Metcalf, C. A. 3rd. (2017) Structure-based discovery of LpxC inhibitors. Bioorg. Med. Chem. Lett. 27, 1670-1680.

3.     Leandro, J., Stokka, A. J., Teigen, K., Andersen, O. A. & Flatmark, T. (2017) Substituting Tyr138 in the active site loop of human phenylalanine hydroxylase affects catalysis and substrate activation. FEBS Open Bio. 7, 1026-1036.

4.     Cross, J. B., Zhang, J., Yang, Q., Mesleh, M. F., Romero, J. A. C., Wang, B., Bevan, D., Poutsiaka, K. M., Epie, P., Moy, T., Daniel, A., Shotwell, J., Chamberlain, B., Carter, N., Andersen, O., Barker, J., Ryan, M. D., Metcalf, III, C. A., Silverman, J., Nguyen, K., Lippa, B. & Dolle, R. (2016) Discovery of Pyrazolopyridones as a Novel Class of Gyrase B Inhibitors Using Structure Guided Design. ACS Med. Chem. Lett. 16, 374-378.

5.     Mesleh, M. F., Cross, J. B., Zhang, J., Kahmann, J., Andersen, O. A., Barker, J., Cheng, R. K., Felicetti, B., Wood, M., Hadfield, A. T., Scheich, C., Moy, T. I., Yang, Q., Shotwell, J., Nguyen, K., Lippa, B., Dolle, R. & Ryan, M. D. (2016) Fragment-based discovery of DNA gyrase inhibitors targeting the ATPase subunit of GyrB. Bioorg. Med. Chem. Lett. 26, 1314-1318.

6.     Prime, M. E., Andersen, O. A., Barker, J. J., Brooks, M. A., Cheng, R. K., Toogood-Johnson, I., Courtney, S. M., Brookfield, F. A., Yarnold, C. J., Marston, R. W., Johnson, P. D., Johnsen, S. F., Palfrey, J. J., Vaidya, D., Erfan, S., Ichihara, O., Felicetti, B., Palan, S., Pedret-Dunn, A., Schaertl, S., Sternberger, I., Ebneth, A., Scheel, A., Winkler, D., Toledo-Sherman, L., Beconi, M., Macdonald, D., Muñoz-Sanjuan, I., Dominguez, C. & Wityak, J. (2012) Discovery and structure-activity relationship of potent and selective covalent inhibitors of transglutaminase 2 for Huntington's disease. J. Med. Chem. 55, 1021-1046.

7.     Sutherland, T. E., Andersen, O. A., Betou, M., Eggleston, I. M., Maizels, R. M., van Aalten, D. & Allen, J. E. (2011) Analyzing airway inflammation with chemical biology: Dissection of acidic mammalian chitinase function with a selective drug-like inhibitor. Chem. Biol. 18, 569-579.

8.     Schüttelkopf, A. W., Andersen, O. A., Rao, F. V., Allwood, M., Rush, C. L., Eggleston, I. M. & van Aalten, D. M. F. (2011) Bisdionin C - a rationally designed, submicromolar inhibitor of family 18 chitinases. ACS Med. Chem. Lett. 2, 428–432.

9.     Andersen, O. A., Schönfeld, D. L., Toogood-Johnson, I, Felicetti, B., Albrecht, C., Fryatt, T., Whittaker, M., Hallett, D. & Barker, J. (2009) Cross-linking of protein crystals as an aid in the generation of binary protein-ligand crystal complexes, exemplified by the human PDE10a-papaverine structure. Acta Crystallog. Sect. D65, 872-874.

10.   Law, R., Barker, O., Barker, J. J., Hesterkamp, T., Godemann, R., Andersen, O., Fryatt, T., Courtney, S., Hallett, D. & Whittaker M. (2009) The multiple roles of computational chemistry in fragment-based drug design. J. Comput. Aided Mol. Des. 23, 459-473.

11.   Dixon, M. J., Nathubhai, A., Andersen, O. A., van Aalten, D. M. F. & Eggleston, I. M. (2009) Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors: new leads for antifungal and anti-inflammatory drugs. Adv. Exp. Med. Biol. 611, 525-526.

12.   Dixon, M. J., Andersen, O. A., van Aalten, D. M. F. & Eggleston, I. M. (2009) SPPS of the natural product chitinase inhibitor argifin: library generation and biological evaluation. Adv. Exp. Med. Biol. 611, 143-144.

13.   Dixon, M. J., Nathubhai, A., Andersen, O. A., van Aalten, D. M. F. & Eggleston, I. M. (2009) Solid-phase synthesis of cyclic peptide chitinase inhibitors: SAR of the argifin scaffold. Org. Biomol. Chem. 7, 259-268.

14.   Andersen, O. A., Nathubhai, A., Dixon, M. J., Eggleston, I. M. & van Aalten, D. M. F. (2008) Structure-based dissection of the natural product cyclopentapeptide chitinase inhibitor argifin. Chem. Biol. 15, 295-301.

15.   Leiros, I., Nabong, M. P., Grøsvik, K., Ringvoll, J., Haugland, G. Y., Uldal, L., Reite, K., Olsbu, I. K., Knævelsrud, I., Moe, E., Andersen, O. A., Birkeland, N.-K., Ruoff, P., Klungland, A. & Bjelland, S. (2007) Structural basis for enzymatic excision of N1-methyladenine and N3-methylcytosine from DNA. EMBO J. 26, 2206-2217.

16.   Wang, E., Koutsioulis, D., Schrøder Leiros, H.-K., Andersen, O. A., Bouriotis, V., Hough, E. & Heikinheimo, P. (2007) Structure of Alkaline Phosphatase from the Antarctic Bacterium TAB5. J. Mol. Biol. 366, 1318-1331.

17.   Dixon, M. J., Andersen, O. A., van Aalten, D. M. F. & Eggleston, I. M. (2006) First synthesis of argadin: a nanomolar inhibitor of family 18 chitinases. Eur. J. Org. Chem. 22, 5002-5006.

18.   Schüttelkopf, A., Andersen, O. A., Rao, F. V., Allwood, M., Lloyd, C. M., Eggleston, I. M. & van Aalten, D. M. F. (2006) Screening-based discovery and structural dissection of a novel family 18 chitinase inhibitor. J. Biol. Chem. 281, 27278-27285.

19.   Andersen, O. A., Dixon, M. J., Eggleston, I. M. & van Aalten, D. M. F. (2005) Natural product family 18 chitinase inhibitors. Natural Product Reports 22, 563-579.

20.   Dixon, M. J., Andersen, O. A., van Aalten, D. M. F. & Eggleston, I. M. (2005) An efficient synthesis of argifin: A natural product chitinase inhibitor with chemotherapeutic potential. Bioorg. Med. Chem. Lett. 15, 4717-4721.

21.   Rao, F. V., Andersen, O. A., Vora, K. A., DeMartino, J. A. & van Aalten, D. M. F. (2005) Methylxanthine drugs are chitinase inhibitors: Investigation of inhibition and binding modes. Chem. & Biol. 12, 973-980.

22.   Schrøder Leiros, H.-K., Brandsdal, B. O., Andersen, O. A., Os, V., Leiros, I., Helland, R., Otlewski, J., Willassen, N. P. & Smalås, A. O. (2004) Trypsin specificity as elucidated by LIE calculations, X-ray structures and association constant measurements. Protein Science 13, 1056-1070.

23.   Andersen, O. A., Hough, E. & Flatmark, T. (2004) Structural insights into the catalytic mechanism of mammalian phenylalanine hydroxylase. In Pterins, folates, and related biogenic amines (Blau, N & Thöny, B. eds) SPS Publications, Heilbronn, Germany. SPS Verlagsgesellschaft mbH 2004. 148-154.

24.   Andersen, O. A., Stokka, A. J., Flatmark, T. & Hough, E. (2003) 2.0 Å resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine or L-norleucine. Substrate specificity and molecular motions related to substrate binding. J. Mol. Biol. 333, 747-757.

25.   Solstad, T., Stokka, A. J., Andersen, O. A. & Flatmark, T. (2003) Studies on the regulatory properties of the pterin cofactor and dopamine bound at the active site of human phenylalanine hydroxylase. Eur. J. Biochem. 270, 981-990.

26.   Solstad, T., Carvalho, R. N., Andersen, O. A., Waidelich, D. & Flatmark, T. (2003) Deamidation of labile asparagine residues in the autoregulatory sequence of human phenylalanine hydroxylase. Structural and functional implications. Eur. J. Biochem. 270, 929-938.

27.   Andersen, O. A., Flatmark, T. & Hough, E. (2002) Crystal structure of the ternary complex of the catalytic domain of human phenylalanine hydroxylase with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine, and its implications for the mechanism of catalysis and substrate activation. J. Mol. Biol. 320, 1095-1108.

28.   Andersen, O. A., Flatmark, T. & Hough, E. (2001) High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J. Mol. Biol. 314, 279-291.

29.   Helland, R., Berglund, G. I., Otlewski, J., Apostoluk, W. A., Andersen, O. A., Willassen, N. P. & Smalås, A. O. (1999) High-resolution structures of three new trypsin-squash-inhibitor complexes: A detailed comparison with other trypsins and their complexes. Acta Crystallog. Sect. D55, 139-148.