Novel Design of Neuropeptide-Based Drugs with β-Sheet Breaking Potential in Amyloid-Beta Cascade: Molecular and Structural Deciphers
Abstract
:1. Introduction
2. Results
2.1. Analysis of Pharmacological Properties
2.2. Bioactivity Screening
2.3. Structural Interaction and Docking
2.4. Solid-Phase Peptide Synthesis (SPPS)
2.5. Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC)
2.6. MALDI-ToF/ToFMass Spectrometry
2.7. Theoretical Circular Dichroism
3. Discussion
4. Materials and Methods
4.1. Estimation of the Pharmacological Properties
4.2. Bioactivity Screening
4.3. Structural Interaction and Docking
4.4. Solid-Phase Peptide Synthesis (SPPS)
4.5. Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC)
4.6. MALDI-ToF Mass Spectrometry
4.7. Circular Dichroism
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Time (min) | % A (0.1% TFA) | % B (80% AcCN in 0.1% TFA, v/v) |
---|---|---|
0 | 95 | 5 |
2 | 95 | 5 |
30 | 0 | 100 |
35 | 0 | 100 |
40 | 95 | 5 |
43 | 95 | 5 |
Peptide | Purity (%) |
---|---|
17LVFF20 | 73.94 |
NA-17LVFF20 | 83.52 |
16KLVF19 | 66.02 |
NA-16KLVF19 | 78.96 |
Peptide | α-Helix Conformation (%) | β-Sheet Conformation (%) | Random Coil Conformation (%) |
---|---|---|---|
17LVFF20 | 2.78 | 52.78 | 44.44 |
NA-17LVFF20 | 0.00 | 56.14 | 43.86 |
16KLVF19 | 0.00 | 67.57 | 32.43 |
NA-16KLVF19 | 5.05 | 38.38 | 56.57 |
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Code | OC | Code | OC | Code | OC | Code | OC | Code | OC | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Peptide ↓ | Peptide ↓ | Peptide ↓ | Peptide ↓ | Peptide ↓ | ||||||||||
1-1 | 1 | 1 | 2-1 | 2 | 1 | 3-1 | 3 | 1 | 4-1 | 4 | 1 | 5-1 | 5 | 1 |
1-2 | 1 | 2 | 2-2 | 2 | 2 | 3-2 | 3 | 2 | 4-2 | 4 | 2 | 5-2 | 5 | 2 |
1-3 | 1 | 3 | 2-3 | 2 | 3 | 3-3 | 3 | 3 | 4-3 | 4 | 3 | 5-3 | 5 | 3 |
1-4 | 1 | 4 | 2-4 | 2 | 4 | 3-4 | 3 | 4 | 4-4 | 4 | 4 | 5-4 | 5 | 4 |
1-5 | 1 | 5 | 2-5 | 2 | 5 | 3-5 | 3 | 5 | 4-5 | 4 | 5 | 5-5 | 5 | 5 |
1-6 | 1 | 6 | 2-6 | 2 | 6 | 3-6 | 3 | 6 | 4-6 | 4 | 6 | 5-6 | 5 | 6 |
1-7 | 1 | 7 | 2-7 | 2 | 7 | 3-7 | 3 | 7 | 4-7 | 4 | 7 | 5-7 | 5 | 7 |
1-8 | 1 | 8 | 2-8 | 2 | 8 | 3-8 | 3 | 8 | 4-8 | 4 | 8 | 5-8 | 5 | 8 |
1-9 | 1 | 9 | 2-9 | 2 | 9 | 3-9 | 3 | 9 | 4-9 | 4 | 9 | 5-9 | 5 | 9 |
1-10 | 1 | 10 | 2-10 | 2 | 10 | 3-10 | 3 | 10 | 4-10 | 4 | 10 | 5-10 | 5 | 10 |
1-11 | 1 | 11 | 2-11 | 2 | 11 | 3-11 | 3 | 11 | 4-11 | 4 | 11 | 5-11 | 5 | 11 |
1-12 | 1 | 12 | 2-12 | 2 | 12 | 3-12 | 3 | 12 | 4-12 | 4 | 12 | 5-12 | 5 | 12 |
1-13 | 1 | 13 | 2-13 | 2 | 13 | 3-13 | 3 | 13 | 4-13 | 4 | 13 | 5-13 | 5 | 13 |
1-14 | 1 | 14 | 2-14 | 2 | 14 | 3-14 | 3 | 14 | 4-14 | 4 | 14 | 5-14 | 5 | 14 |
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Mocanu, C.S.; Niculaua, M.; Zbancioc, G.; Mangalagiu, V.; Drochioiu, G. Novel Design of Neuropeptide-Based Drugs with β-Sheet Breaking Potential in Amyloid-Beta Cascade: Molecular and Structural Deciphers. Int. J. Mol. Sci. 2022, 23, 2857. https://doi.org/10.3390/ijms23052857
Mocanu CS, Niculaua M, Zbancioc G, Mangalagiu V, Drochioiu G. Novel Design of Neuropeptide-Based Drugs with β-Sheet Breaking Potential in Amyloid-Beta Cascade: Molecular and Structural Deciphers. International Journal of Molecular Sciences. 2022; 23(5):2857. https://doi.org/10.3390/ijms23052857
Chicago/Turabian StyleMocanu, Cosmin Stefan, Marius Niculaua, Gheorghita Zbancioc, Violeta Mangalagiu, and Gabi Drochioiu. 2022. "Novel Design of Neuropeptide-Based Drugs with β-Sheet Breaking Potential in Amyloid-Beta Cascade: Molecular and Structural Deciphers" International Journal of Molecular Sciences 23, no. 5: 2857. https://doi.org/10.3390/ijms23052857