Biophysical Society Thematic Meeting - October 25-30, 2015

Polymers and Self Assembly: From Biology to Nanomaterials Poster Session II

7-POS Board 7 Amyloid Self-Assembly of Insulin in Presence of Glyco-Acridines: In Vitro and In Silico Study Zuzana Bednarikova 1,2 , Quan Van Vuong 3 , Andrea Antosova 1 , Pham Dinh Quoc Huy 3,4 , Katarina Siposova 1 , Nguyen Anh Tuan 5 , Suan Li Mai 3,4 , Zuzana Gazova 1 . 1 Institute of Experimental Physics, Slovak Academy of Sciences, Kosice, Slovakia, 2 Faculty of Science, Safarik University, Kosice, Slovakia, 3 Institute for Computational Science and Technology, Tan Chanh Hiep Ward, Ho Chi Minh City, District 12, Viet Nam, 4 Institute of Physics Polish Academy of Sciences, Warsaw, Poland, 5 University of Science - VNUHCM, Ho Chi Minh City, Viet Nam. Self-assembly of insulin into amyloid aggregates causes problems in the insulin production, storage and application of insulin pumps. Frequent application of insulin into patients with diabetes may result in formation of deposits consisting of insulin amyloid aggregates. We have investigated the effect of 9 aromatic glyco-acridine derivatives with side saccharide chain connected by different linkers on insulin amyloid self-assembly using ThT assay, FTIR spectroscopy and AFM technique. Our results indicate that glyco-acridines are able to interfere with amyloid self-assembling of insulin depending on their structure. The most effective inhibitory effect was obtained for isothiosemicarbazide derivate I1. The obtained IC 50 value was in µM range. The least effective were thiosemicarbazide and cyclic 1,3-thiazolidinone derivatives. In silico calculation point out that the non-polar interactions together with the core of acridine derivatives are the key factors determining ligand's free binding energy to insulin. The contribution of the linker and side chains to the inhibitory activity depends not only on their position relative to the core but also on their flexibility. Our findings can be useful for the design of new small molecule drugs for therapy of amyloid-related diseases. This work was supported by the projects VEGA0181, EU26110230097, Narodowe Centrum Nauki in Poland (2011/01/B/NZ1/01622), Vietnam National Foundation for Science and Technology Development (NAFOSTED-106-YS.02-2013.01).

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