The quest for the shortest fragments of A (13–19) and B (12–17) responsible for the aggregation of human insulin
| Autor: | Zbigniew J. Kaminski, Justyna Fraczyk, Monika Swiontek, Kamil Rozniakowski, Wojciech Lipinski, Beata Kolesinska, Stanisław Wysocki, Krystian Gałęcki, Bertrand G. R. Dupont |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Amyloid Stereochemistry medicine.medical_treatment Biomedical Engineering Medicine (miscellaneous) Bioengineering Development Protein aggregation Protein Aggregation Pathological 01 natural sciences Hydrophobic effect Protein Aggregates 03 medical and health sciences Residue (chemistry) Leucine medicine Humans Insulin General Materials Science Amino Acid Sequence Tyrosine Peptide sequence 010405 organic chemistry Chemistry Peptide Fragments 0104 chemical sciences 030104 developmental biology Biochemistry Function (biology) |
| Zdroj: | Nanomedicine. 11:2083-2101 |
| ISSN: | 1748-6963 1743-5889 |
| DOI: | 10.2217/nnm-2016-0100 |
| Popis: | Aim: To identify the shortest components of A13-A19, B12-B17 fragments capable for fibrillation and to validate the dependability of aggregation on the presence of hydroxyl group engaged in the ‘tyrosine kissing’. Materials & methods: Fragments A13-A19 and B12-B17 of insulin and all shortened analogues were obtained by using DMT/NMM/TosO- as a coupling reagent. The aggregation was studied by three independent tests. Results: Studies on the susceptibility to aggregation of truncated analogs of insulin amyloidogenic core show three groups of peptides. Conclusion: Truncation of A13-A419 fragment shows that fibrous structures are formed by all peptides bearing 13H-LeuTyr-OH14. Propensity to aggregation was found for 16H-TyrLeu-OH17 B12-B17 fragment. Tyrosine residue modification by incorporation of tert-butyl group on hydroxyl function gave analogues still predisposed to aggregation. |
| Databáze: | OpenAIRE |
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