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Nanomedical Relevance of the Intermolecular Interaction Dynamics - Examples from Lysozymes and Insulins

Journal article
Authors Ruiyan Zhang
Ning Zhang
Marzieh Mohri
Lisha Wu
Thomas Eckert
Vadim B. Krylov
Andrea Antosova
Slavomira Ponikova
Zuzana Bednarikova
Philipp Markart
Andreas Günther
Bengt Norden
Martin Billeter
Robert Schauer
Axel J. Scheidig
Bhisma N. Ratha
Anirban Bhunia
Kartsen Hesse
Mushira Abdelaziz Enani
Jürgen Steinmeyer
Athanasios K. Petridis
Tibor Kozar
Zuzana Gazova
Nikolay E. Nifantiev
Hans-Christian Siebert
Published in ACS Omega
Volume 4
Pages 4206-4220
ISSN 2470-1343
Publication year 2019
Published at Department of Chemistry and Molecular Biology
Pages 4206-4220
Language en
Links https://pubs.acs.org/doi/10.1021/ac...
Subject categories Structural Biology

Abstract

Insulin 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 ogether, the data accumulated and knowledge gained will further facilitate nanoparticle design and production with insulin or lysozyme-related protein encapsulation.

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