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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).