The Interaction of Possible Anti-AD ASA-NAP Peptide Conjugate with Tubulin: A Theoretical and Experimental Insight
| Autor: | Cosmin Stefan Mocanu, Gabi Drochioiu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
In silico fungi Bioengineering Peptide Biochemistry Analytical Chemistry Amino acid Nap chemistry.chemical_compound chemistry Acetylation mental disorders Drug Discovery Peptide synthesis Biophysics Molecular Medicine Linker psychological phenomena and processes Conjugate |
| Zdroj: | International Journal of Peptide Research and Therapeutics. 27:2487-2503 |
| ISSN: | 1573-3904 1573-3149 |
| Popis: | NAP peptide (1NAPVSIPQ8) is a small active fragment of the activity-dependent neuroprotective protein, which provides a neuroprotective role at low concentrations. Therefore, NAP-derived peptides might be of scientific and clinical interest because they could provide neuro and cognitive protection of the brain. In this study, we report the use of sonication in the Fmoc strategy allows to reduce the time of synthesis of NAP peptide conjugate with acetylsalicylic acid (ASA-NAP). The theoretical data suggest that both NAP and ASA-NAP can coexist together in a system that does not need to be replaced by each other, like NAP on paclitaxol. Moreover, ASA-NAP could follow the same molecular interaction pattern as NAP in the case of end-binding proteins (EB) and Tau involvement. In addition, the effect that these peptides possess can be cumulated, thus improving the neuroprotective action. Furthermore, we have studied the differences between the classical synthesis (SPPS) and the classical method using ultrasound (SPPS-U). This improvement may be a promising alternative to the traditional SPPS method and that of microwave-based synthesis. The use of ultrasound during peptide synthesis and the influence of sonication on the final products are also discussed. In addition, mass spectrometry analysis suggests that under SPPS-U, processes of deacetylation, deamination and demethylation of the etheric group of resin linker, incomplete cleavage of tertbutyl and incomplete process of amino acids coupling occurs. The innovation of our work brings together the advantages of both ultrasounds assisted techniques and in silico studies in order to bring improvements on the structural and biocompatibility of peptide-based drugs such as ASA-NAP, finally enhancing therapy pathways for Alzheimer disease. |
| Databáze: | OpenAIRE |
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