Search

Your search keyword '"Saravanan, Manikam S"' showing total 4 results
Start Over Author "Saravanan, Manikam S"
4 results on '"Saravanan, Manikam S"'

2. The small molecule inhibitor anle145c thermodynamically traps human islet amyloid peptide in the form of non-cytotoxic oligomers

Author

Saravanan, Manikam S, Ryazanov, Sergey, Leonov, Andrei, Nicolai, Janine, Praest, Patrique, Giese, Armin, Winter, Roland, Khemtemourian, Lucie, Griesinger, Christian, Killian, J Antoinette, Saravanan, Manikam S, Ryazanov, Sergey, Leonov, Andrei, Nicolai, Janine, Praest, Patrique, Giese, Armin, Winter, Roland, Khemtemourian, Lucie, Griesinger, Christian, and Killian, J Antoinette

Abstract

Type 2 diabetes (T2DM) is associated with aggregation of the human islet amyloid polypeptide (hIAPP) into cytotoxic amyloid species. Here we tested the effect of a diphenylpyrazole (DPP)-derived small molecule inhibitor, anle145c, on cytotoxicity and on aggregation properties of hIAPP. We demonstrate that incubation of hIAPP with the inhibitor yields ~10 nm-sized non-toxic oligomers, independent of the initial aggregation state of hIAPP. This suggests that anle145c has a special mode of action in which anle145c-stabilized oligomers act as a thermodynamic sink for the preferred aggregation state of hIAPP and anle145c. We also demonstrate that the inhibitor acts in a very efficient manner, with sub-stoichiometric concentrations of anle145c being sufficient to (i) inhibit hIAPP-induced death of INS-1E cells, (ii) prevent hIAPP fibril formation in solution, and (iii) convert preformed hIAPP fibrils into non-toxic oligomers. Together, these results indicate that anle145c is a promising candidate for inhibition of amyloid formation in T2DM.

Published
2019

3. The small molecule inhibitor anle145c thermodynamically traps human islet amyloid peptide in the form of non-cytotoxic oligomers

Author

Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Saravanan, Manikam S, Ryazanov, Sergey, Leonov, Andrei, Nicolai, Janine, Praest, Patrique, Giese, Armin, Winter, Roland, Khemtemourian, Lucie, Griesinger, Christian, Killian, J Antoinette, Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Saravanan, Manikam S, Ryazanov, Sergey, Leonov, Andrei, Nicolai, Janine, Praest, Patrique, Giese, Armin, Winter, Roland, Khemtemourian, Lucie, Griesinger, Christian, and Killian, J Antoinette

Published
2019

4. The small molecule inhibitor anle145c thermodynamically traps human islet amyloid peptide in the form of non-cytotoxic oligomers

Author

MMB Research line 3a, Saravanan, Manikam S., Ryazanov, Sergey, Leonov, Andrei, Nicolai, Janine, Praest, Patrique, Giese, Armin, Winter, Roland, Khemtemourian, Lucie, Griesinger, Christian, Killian, J. Antoinette, MMB Research line 3a, Saravanan, Manikam S., Ryazanov, Sergey, Leonov, Andrei, Nicolai, Janine, Praest, Patrique, Giese, Armin, Winter, Roland, Khemtemourian, Lucie, Griesinger, Christian, and Killian, J. Antoinette

Published
2019

Catalog

Books, media, physical & digital resources
See catalog results