Daniel E Otzen



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    Otzen D. Amyloid formation in surfactants and alcohols: membrane mimetics or structural switchers?. Curr Protein Pept Sci. 2010;11:355-71 pubmed
  2. Mohammad Beigi H, Shojaosadati S, Marvian A, Pedersen J, Klausen L, Christiansen G, et al. Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics. Nanoscale. 2015;7:19627-40 pubmed publisher
    ..Collectively, our results highlight the fact that a simple modification of NPs can strongly modulate interactions with target proteins, which may have important and positive implications in NP safety. ..
  3. Mohammad Beigi H, Aliakbari F, Sahin C, Lomax C, Tawfike A, Schafer N, et al. Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity. J Biol Chem. 2019;294:4215-4232 pubmed publisher
    ..Our results highlight the molecular consequences of differences in the level of effective phenolic compounds in different olive varieties, insights that have implications for long-term human health. ..
  4. Pedersen J, Jiang Z, Christiansen G, Lee J, Pedersen J, Otzen D. Lysophospholipids induce fibrillation of the repeat domain of Pmel17 through intermediate core-shell structures. Biochim Biophys Acta Proteins Proteom. 2018;: pubmed publisher
    ..Nevertheless, LPC only promotes aggregation above the cmc and this process is not inhibited by high LPC concentrations, suggesting that monomers and micelles cooperate to influence amyloid formation. ..
  5. Højgaard C, Sørensen H, Pedersen J, Winther J, Otzen D. Can a Charged Surfactant Unfold an Uncharged Protein?. Biophys J. 2018;115:2081-2086 pubmed publisher
  6. Madsen J, Giehm L, Otzen D. The Use of Surfactants to Solubilise a Glucagon Analogue. Pharm Res. 2018;35:235 pubmed publisher
    ..Stronger enthalpic interactions improved the absolute solubility of ZP-GA-1 and their strength correlated to the absolute solubility of the peptides though not to the kinetics of precipitation. ..
  7. Kurnik M, Sahin C, Andersen C, Lorenzen N, Giehm L, Mohammad Beigi H, et al. Potent α-Synuclein Aggregation Inhibitors, Identified by High-Throughput Screening, Mainly Target the Monomeric State. Cell Chem Biol. 2018;25:1389-1402.e9 pubmed publisher
    ..We also identified several phenyl-benzoxazol compounds that promoted αSN aggregation (proaggregators). These compounds may be useful tools to modulate αSN aggregation in cellula. ..
  8. Otzen D. Mapping the folding pathway of the transmembrane protein DsbB by protein engineering. Protein Eng Des Sel. 2011;24:139-49 pubmed publisher
    ..5 forms at one end of the transmembrane helices, which expands to include residues closer to the middle of the protein in I. Thus, folding proceeds from a highly polarized starting point. ..
  9. Christoffersen H, Andreasen M, Zhang S, Nielsen E, Christiansen G, Dong M, et al. Scaffolded multimers of hIAPP(20-29) peptide fragments fibrillate faster and lead to different fibrils compared to the free hIAPP(20-29) peptide fragment. Biochim Biophys Acta. 2015;1854:1890-1897 pubmed publisher
    ..Thus the motional restrictions introduced by the scaffold modulate the structure of the fibrils but do not impede the actual fibrillation process. ..

More Information


  1. Andersen K, Otzen D. Denaturation of ?-lactalbumin and myoglobin by the anionic biosurfactant rhamnolipid. Biochim Biophys Acta. 2014;1844:2338-45 pubmed publisher
    ..These features restrict the concentration range where RL monomers can bind and denature proteins while still allowing micelles to bind and denature to a significant extent. ..
  2. Christoffersen H, Hansen S, Vad B, Nielsen E, Nielsen J, Vosegaard T, et al. The natural, peptaibolic peptide SPF-5506-A4 adopts a β-bend spiral structure, shows low hemolytic activity and targets membranes through formation of large pores. Biochim Biophys Acta. 2015;1854:882-9 pubmed publisher
    ..6 nm diameter) fluorescence-labeled dextran from vesicles while leaving the vesicles intact. We conclude that SPF-5506-A(4) follows the toroidal pore model in its mode of action. ..
  3. Madsen J, Sørensen T, Kaspersen J, Silow M, Vind J, Pedersen J, et al. Promoting protein self-association in non-glycosylated Thermomyces lanuginosus lipase based on crystal lattice contacts. Biochim Biophys Acta. 2015;1854:1914-1921 pubmed publisher
    ..We conclude that crystal lattice contacts are a good starting point for design strategies to promote protein self-association. ..
  4. Stenvang M, Schafer N, Malmos K, Pérez A, Niembro O, Sormanni P, et al. Corneal Dystrophy Mutations Drive Pathogenesis by Targeting TGFBIp Stability and Solubility in a Latent Amyloid-forming Domain. J Mol Biol. 2018;430:1116-1140 pubmed publisher
    ..Thus, TGFBIp aggregation is driven by mutations that despite their physico-chemical diversity target either the stability or solubility of Fas1-4 in predictable ways, suggesting straightforward general therapeutic strategies. ..
  5. Brinkmann C, Thiel S, Otzen D. Protein-fatty acid complexes: biochemistry, biophysics and function. FEBS J. 2013;280:1733-49 pubmed publisher
    ..Further studies will aim to determine how the molecular properties of the different protein-lipid complexes correlate with their biological efficacy. ..
  6. Frislev H, Nielsen J, Nylandsted J, Otzen D. Using Liprotides to Deliver Cholesterol to the Plasma Membrane. J Membr Biol. 2018;251:581-592 pubmed publisher
    ..Further, cytotoxicity is strongly reduced when OA is replaced by cis-palmitoleic acid or cis-vaccenic acid. This makes liprotides good tools to deliver chol to membranes and cells. ..
  7. Andreasen M, Lorenzen N, Otzen D. Interactions between misfolded protein oligomers and membranes: A central topic in neurodegenerative diseases?. Biochim Biophys Acta. 2015;1848:1897-907 pubmed publisher
    ..This article is part of a Special Issue entitled: Lipid-protein interactions. ..
  8. Bleem A, Christiansen G, Madsen D, Maric H, Strømgaard K, Bryers J, et al. Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms. J Mol Biol. 2018;430:3751-3763 pubmed publisher
    ..The insights reported here expand our understanding of the mechanism of amyloid polymerization in P. aeruginosa, laying the foundation for development of new amyloid inhibitors to combat recalcitrant biofilm infections. ..
  9. Otzen D. Biosurfactants and surfactants interacting with membranes and proteins: Same but different?. Biochim Biophys Acta Biomembr. 2017;1859:639-649 pubmed publisher
    ..This article is part of a Special Issue entitled: Lipid order/lipid defects and lipid-control of protein activity edited by Dirk Schneider. ..
  10. Pedersen J, Sørensen H, Otzen D. Stabilizing vitamin D3 using the molten globule state of ?-lactalbumin. J Dairy Sci. 2018;101:1817-1826 pubmed publisher
    ..This study demonstrates the potential of ?-LA as a component in vitD fortification, particularly for low pH applications. ..
  11. Pedersen J, Frislev H, Pedersen J, Otzen D. Using protein-fatty acid complexes to improve vitamin D stability. J Dairy Sci. 2016;99:7755-7767 pubmed publisher
    ..Our results indicate that vitD may be encapsulated and stabilized for enrichment of clear beverages at neutral pH to improve the intake and bioavailability of vitD. ..
  12. Malmos K, Bjerring M, Jessen C, Nielsen E, Poulsen E, Christiansen G, et al. How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin. J Biol Chem. 2016;291:16849-62 pubmed publisher
  13. Hjorth C, Norrman M, Wahlund P, Benie A, Petersen B, Jessen C, et al. Structure, Aggregation, and Activity of a Covalent Insulin Dimer Formed During Storage of Neutral Formulation of Human Insulin. J Pharm Sci. 2016;105:1376-86 pubmed publisher
    ..In addition, increasing amounts of HMWP reduce the rate of insulin fibrillation. ..
  14. Paslawski W, Lorenzen N, Otzen D. Formation and Characterization of α-Synuclein Oligomers. Methods Mol Biol. 2016;1345:133-50 pubmed publisher
    ..Also, we briefly discuss a selection of biophysical methods which allow for a quick characterization of oligomer purity and structure. ..
  15. Mortensen H, Madsen J, Andersen K, Vosegaard T, Deen G, Otzen D, et al. Myoglobin and α-Lactalbumin Form Smaller Complexes with the Biosurfactant Rhamnolipid Than with SDS. Biophys J. 2017;113:2621-2633 pubmed publisher
    ..The results highlight how RL and SDS follow similar overall rules of self-assembly and interactions with proteins, but that differences in the strength of protein-surfactant interactions affect the formed structures. ..
  16. Christiansen S, Zhang X, Juul Madsen K, Hvam M, Vad B, Behrens M, et al. The random co-polymer glatiramer acetate rapidly kills primary human leukocytes through sialic-acid-dependent cell membrane damage. Biochim Biophys Acta Biomembr. 2017;1859:425-437 pubmed publisher
    ..The comparison of LL-37 and GA highlights a consistent requirement of certain oligomeric and chemical properties to support cytotoxic effects of cationic polymers targeting human leukocytes. ..
  17. Kaspersen J, Søndergaard A, Madsen D, Otzen D, Pedersen J. Refolding of SDS-Unfolded Proteins by Nonionic Surfactants. Biophys J. 2017;112:1609-1620 pubmed publisher
    ..We conclude that NIS competes with globular proteins for association with SDS, making it possible to release and refold SDS-denatured proteins by adding sufficient amounts of NIS, unless the protein also interacts with NIS alone. ..
  18. Lorenzen N, Lemminger L, Pedersen J, Nielsen S, Otzen D. The N-terminus of ?-synuclein is essential for both monomeric and oligomeric interactions with membranes. FEBS Lett. 2014;588:497-502 pubmed publisher
    ..We attribute oligomer permeabilization both to cooperative electrostatic interactions through the N-terminus and interactions mediated by hydrophobic regions in the oligomer. ..
  19. Sørensen H, Pedersen J, Pedersen J, Otzen D. Tailoring thermal treatment to form liprotide complexes between oleic acid and different proteins. Biochim Biophys Acta Proteins Proteom. 2017;1865:682-693 pubmed publisher
    ..Our SAXS-based approach provides a straightforward strategy to optimize liprotide formation for a wide range of different proteins. ..
  20. Otzen D, Blans K, Wang H, Gilbert G, Rasmussen J. Lactadherin binds to phosphatidylserine-containing vesicles in a two-step mechanism sensitive to vesicle size and composition. Biochim Biophys Acta. 2012;1818:1019-27 pubmed publisher
    ..We conclude that the vesicular environment provides optimal conditions for presentation and recognition of PS by lactadherin in a simple binding mechanism. This article is part of a Special Issue entitled: Protein Folding in Membranes...
  21. Frislev H, Boye T, Nylandsted J, Otzen D. Liprotides kill cancer cells by disrupting the plasma membrane. Sci Rep. 2017;7:15129 pubmed publisher
    ..We conclude that MCF7 cells counteract liprotide-induced membrane permeabilization by activating their plasma membrane repair system, which is triggered by extracellular Ca2+ and involves ANXA6. ..
  22. Sahin C, Lorenzen N, Lemminger L, Christiansen G, Møller I, Vesterager L, et al. Antibodies against the C-terminus of ?-synuclein modulate its fibrillation. Biophys Chem. 2017;220:34-41 pubmed publisher
    ..This suggests that the development of antibodies that targets the C-terminus, exposed in the aggregated forms of aSN, may be beneficial for improved immunotherapy against PD. ..
  23. Stenvang M, Dueholm M, Vad B, Seviour T, Zeng G, Geifman Shochat S, et al. Epigallocatechin Gallate Remodels Overexpressed Functional Amyloids in Pseudomonas aeruginosa and Increases Biofilm Susceptibility to Antibiotic Treatment. J Biol Chem. 2016;291:26540-26553 pubmed
    ..Our results provide a direct molecular explanation for the ability of EGCG to disrupt P. aeruginosa QS and modify its biofilm and strengthens the case for EGCG as a candidate in multidrug treatment of persistent biofilm infections. ..
  24. Madsen J, Hjørringgaard C, Vad B, Otzen D, Skrydstrup T. Incorporation of ?-Silicon-?3-Amino Acids in the Antimicrobial Peptide Alamethicin Provides a 20-Fold Increase in Membrane Permeabilization. Chemistry. 2016;22:8358-67 pubmed publisher
    ..The incorporation was shown to provide up to 20-fold increase in calcein release as compared with wild-type alamethicin. ..
  25. Frislev H, Jessen C, Oliveira C, Pedersen J, Otzen D. Liprotides made of ?-lactalbumin and cis fatty acids form core-shell and multi-layer structures with a common membrane-targeting mechanism. Biochim Biophys Acta. 2016;1864:847-59 pubmed publisher
    ..This highlights liprotides as a general class of complexes where both protein and cis-FA component can be varied without departing from a generic (though sometimes multi-layered) core-shell structure. ..
  26. Paslawski W, Lillelund O, Kristensen J, Schafer N, Baker R, Urban S, et al. Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops. Proc Natl Acad Sci U S A. 2015;112:7978-83 pubmed publisher
    ..The origin of the interactions in the transition state that lead to a large number of negative Ï•-values remains to be elucidated. ..
  27. Frislev H, Jakobsen S, Frank S, Otzen D. Dynamic content exchange between liprotides. Biophys Chem. 2018;233:13-18 pubmed publisher
    ..Transfer kinetics was not affected by the presence of the membrane stabilizing lipid cholesterol. Thus, transfer is a remarkably rapid process which illustrates liprotides' efficacy as transporters of hydrophobic compounds. ..
  28. Risør M, Juhl D, Bjerring M, Mathiesen J, Enghild J, Nielsen N, et al. Critical Influence of Cosolutes and Surfaces on the Assembly of Serpin-Derived Amyloid Fibrils. Biophys J. 2017;113:580-596 pubmed publisher
    ..Our study illustrates the versatile thermodynamic landscape of amyloid formation and highlights how different experimental conditions direct C-36 into distinct macromolecular structures. ..
  29. Malmos K, Stenvang M, Sahin C, Christiansen G, Otzen D. The Changing Face of Aging: Highly Sulfated Glycosaminoglycans Induce Amyloid Formation in a Lattice Corneal Dystrophy Model Protein. J Mol Biol. 2017;429:2755-2764 pubmed publisher
    ..Our results highlight a possible role of changing GAG sulfation in the accumulation of amyloid, which also may have implications for the development of neurodegenerative diseases. ..