Structure-Activity Study of an All-d Antimicrobial Octapeptide D2D
Abstract
:1. Introduction
2. Results and Discussion
2.1. Alanine Scan of D2D
2.2. Investigation of Hydrophobicity at Position 5 and 7 Analogues
2.3. Manipulating Amphipaticity and Truncations (Compounds 25–32)
2.4. Manipulating Cationicity by Lys-Arg Substitutions (Compound 33–36)
2.5. Time-kill Kinetics of D2D and Analogue 5
2.6. CD-Experiments
2.7. Peptide Self-Assembly Nanostructure Investigated by Small Angle X-ray Scattering
2.8. Lipid Interaction Probed by Small Angle X-ray Scattering
3. Materials and Methods
3.1. Synthesis of Peptides
3.2. Bacterial Strains
3.3. Antimicrobial Susceptibility Testing
3.4. Time Kill Curves
3.5. Hemolytic Activity
3.6. Circular Dichroism
3.7. Small Angle X-ray Scattering on Pure Peptides in Solution
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Not available. |
Minimum Inhibitory Concentration [a] | ||||||
---|---|---|---|---|---|---|
No. | Sequence [b] | E.C. [c] | S.A. [d] | P.A. [e] | A.B. [f] | %H [g] |
D2D | kk(1-nal)fk(1-nal)k(nle)-NH2 | 8 | 8 | 4 | 4 | 23 |
1 | ak(1-nal)fk(1-nal)k(nle)-NH2 | 8 | 2 | 8 | 4 | 41 |
2 | ka(1-nal)fk(1-nal)k(nle)-NH2 | 16 | 8 | 16 | 16 | 59 |
3 | kkafk(1-nal)k(nle)-NH2 | >128 | 64 | 16 | 16 | 2 |
4 | kk(1-nal)ak(1-nal)k(nle)-NH2 | >128 | 128 | 32 | 64 | 22 |
5 | kk(1-nal)fa(1-nal)k(nle)-NH2 | 4 | 4 | 4 | 4 | 47 |
6 | kk(1-nal)fkak(nle)-NH2 | >128 | >128 | >128 | >128 | 10 |
7 | kk(1-nal)fk(1-nal)a(nle)-NH2 | 8 | 8 | 8 | 4 | 67 |
8 | kk(1-nal)fk(1-nal)ka-NH2 | 64 | 64 | 16 | 64 | 5 |
9 | kk(1-nal)f(1-nal)(1-nal)k(nle)-NH2 | 64 | 4 | 128 | 32 | 20 |
10 | kk(1-nal)f(dap)(1-nal)k(nle)-NH2 | 8 | 16 | 16 | 16 | 28 |
11 | kk(1-nal)f(nle)(1-nal)k(nle)-NH2 | 16 | 4 | 64 | 64 | 33 |
12 | kk(1-nal)ff(1-nal)k(nle)-NH2 | 16 | 4 | 32 | 16 | 74 |
13 | kk(1-nal)fs(1-nal)k(nle)-NH2 | 4 | 8 | 32 | 8 | 29 |
14 | kk(1-nal)ft(1-nal)k(nle)-NH2 | 8 | 8 | 32 | 8 | 28 |
15 | kk(1-nal)fy(1-nal)k(nle)-NH2 | 8 | 2 | 16 | 8 | 40 |
16 | kk(1-nal)fv(1-nal)k(nle)-NH2 | 32 | 4 | 64 | 64 | 54 |
17 | kk(1-nal)fk(1-nal)(1-nal)(nle)-NH2 | 16 | 2 | 32 | 4 | 89 |
18 | kk(1-nal)fk(1-nal)(dap)(nle)-NH2 | 8 | 16 | 16 | 16 | 21 |
19 | kk(1-nal)fk(1-nal)(nle)(nle)-NH2 | 8 | 4 | 32 | 8 | 56 |
20 | kk(1-nal)fk(1-nal)f(nle)-NH2 | 8 | 4 | 32 | 4 | 91 |
21 | kk(1-nal)fk(1-nal)s(nle)-NH2 | 8 | 16 | 64 | 16 | 85 |
22 | kk(1-nal)fk(1-nal)t(nle)-NH2 | 8 | 8 | 32 | 8 | 66 |
23 | kk(1-nal)fk(1-nal)y(nle)-NH2 | 8 | 4 | 64 | 8 | 74 |
24 | kk(1-nal)fk(1-nal)v(nle)-NH2 | 8 | 4 | 32 | 8 | 50 |
25 | kk(1-nal)fkk(1-nal)(nle)-NH2 | 128 | 64 | 32 | 32 | 50 |
26 | kk(1-nal)fk(1-nal)(nle)k-NH2 | 128 | 64 | 32 | 32 | 18 |
27 | k(1-nal)fk(1-nal)k(nle)-NH2 | 8 | 8 | 32 | 16 | 49 |
28 | (1-nal)fk(1-nal)k(nle)-NH2 | >128 | >128 | >128 | >128 | 62 |
29 | fk(1-nal)k(nle)-NH2 | >128 | >128 | 128 | >128 | 12 |
30 | kk(1-nal)fk(1-nal)k-NH2 | >128 | >128 | 128 | >128 | 11 |
31 | kk(1-nal)fk(1-nal)-NH2 | >128 | >128 | 128 | >128 | 20 |
32 | kk(1-nal)fk-NH2 | >128 | >128 | >128 | >128 | 5 |
33 | rk(1-nal)fk(1-nal)k(nle)-NH2 | 8 | 8 | 16 | 16 | 60 |
34 | kr(1-nal)fk(1-nal)k(nle)-NH2 | 8 | 4 | 16 | 16 | 35 |
35 | kk(1-nal)fr(1-nal)k(nle)-NH2 | 8 | 4 | 16 | 16 | 49 |
36 | kk(1-nal)fk(1-nal)r(nle)-NH2 | 8 | 2 | 16 | 8 | 51 |
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Lone, A.; Thomsen, T.T.; Nielsen, J.E.; Thulstrup, P.W.; Klitgaard, R.N.; Løbner-Olesen, A.; Lund, R.; Jenssen, H.; Hansen, P.R. Structure-Activity Study of an All-d Antimicrobial Octapeptide D2D. Molecules 2019, 24, 4571. https://doi.org/10.3390/molecules24244571
Lone A, Thomsen TT, Nielsen JE, Thulstrup PW, Klitgaard RN, Løbner-Olesen A, Lund R, Jenssen H, Hansen PR. Structure-Activity Study of an All-d Antimicrobial Octapeptide D2D. Molecules. 2019; 24(24):4571. https://doi.org/10.3390/molecules24244571
Chicago/Turabian StyleLone, Abdullah, Thomas T. Thomsen, Josefine Eilsø Nielsen, Peter W. Thulstrup, Rasmus N. Klitgaard, Anders Løbner-Olesen, Reidar Lund, Håvard Jenssen, and Paul R. Hansen. 2019. "Structure-Activity Study of an All-d Antimicrobial Octapeptide D2D" Molecules 24, no. 24: 4571. https://doi.org/10.3390/molecules24244571