Nanomedical Relevance of the Intermolecular Interaction Dynamics—Examples from Lysozymes and Insulins
Krylov, Vadim B.
Scheidig, Axel J.
Ratha, Bhisma N.
Enani, Mushira Abdelaziz
Petridis, Athanasios K.
Nifantiev, Nikolay E.
KAUST Grant NumberKUK-11-008-23
Permanent link to this recordhttp://hdl.handle.net/10754/668080
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AbstractInsulin and lysozyme share the common features of being prone to aggregate and having biomedical importance. Encapsulating lysozyme and insulin in micellar nanoparticles probably would prevent aggregation and facilitate oral drug delivery. Despite the vivid structural knowledge of lysozyme and insulin, the environment-dependent oligomerization (dimer, trimer, and multimer) and associated structural dynamics remain elusive. The knowledge of the intra- and intermolecular interaction profiles has cardinal importance for the design of encapsulation protocols. We have employed various biophysical methods such as NMR spectroscopy, X-ray crystallography, Thioflavin T fluorescence, and atomic force microscopy in conjugation with molecular modeling to improve the understanding of interaction dynamics during homo-oligomerization of lysozyme (human and hen egg) and insulin (porcine, human, and glargine). The results obtained depict the atomistic intra- and intermolecular interaction details of the homo-oligomerization and confirm the propensity to form fibrils. Taken together, the data accumulated and knowledge gained will further facilitate nanoparticle design and production with insulin or lysozyme-related protein encapsulation.
CitationZhang, R., Zhang, N., Mohri, M., Wu, L., Eckert, T., Krylov, V. B., … Siebert, H.-C. (2019). Nanomedical Relevance of the Intermolecular Interaction Dynamics—Examples from Lysozymes and Insulins. ACS Omega, 4(2), 4206–4220. doi:10.1021/acsomega.8b02471
SponsorsThis work was supported by the Open Project of Shandong Collaborative Innovation Center for Antibody Drugs (No. CIC-AD1834) and Tai-Shan Scholar Research Fund of Shandong Province of China. This work was also technically supported by Engineering Research Center for Nanomedicine and Drug Delivery Systems. The Swedish NMR Centre is acknowledged for supplying instrument time and support. This work was supported by the King Abdullah University of Science and Technology (grant KUK-11-008-23 awarded to B.N. with Ph.D. position for L.W.) and the European Research Council (ERC-2008-AdG 227700 to B.N.). We thank the Sialic Acids Society for financial support. Parts of the work were supported by RSF grant 14-23-00199 (NEN). On the Slovak side, the work was supported by project VEGA 2/0145/17, 2/0030/18, and SAS-MOST JRP 2015/5. This work was partly supported by Council of Scientific and Industrial Research (CSIR), Govt. of India (02(0292)/17/EMR-II) (to AB). Supports from EU projects 26220120033, 26210120002, 26110230097, and 26210120012 (IEP SAS Kosice, Slovakia) are gratefully acknowledged. We also thank Prof. Dr Frank D Sonnichsen (Otto Diels Institute for Organic Chemistry, Christian Albrechts University, Kiel, Germany) for his helpful support with respect to some of our NMR experiments. Last but not least, Dr Anna Kozarova (University of Windsor, Windsor, Ontario Canada) is highly acknowledged for critical reading and helpful comments on the manuscript.
PublisherAmerican Chemical Society (ACS)