Kiat Hwa Chan1,2, Bo Xue3,4,5, Robert C. Robinson3,5,6 & Charlotte A. E. Hauser1,7
1 Institute of Bioengineering and Nanotechnology, Biopolis, A*STAR (Agency for Science, Technology and Research) Singapore, 138669, Singapore.
2 Division of Science, Yale-NUS College, 16 College Avenue West, Singapore, 138527, Singapore.
3 Institute of Molecular and Cell Biology, Biopolis, A*STAR (Agency for Science, Technology and Research), Singapore, 138673, Singapore.
4 NUS Synthetic Biology for Clinical and Technological Innovation, Centre for Life Sciences, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore.
5 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore, 117597, Singapore.
6 Research Institute for Interdisciplinary Science, Okayama University, Okayama, 700-8530, Japan.
7 Laboratory for Nanomedicine, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia.
Published online in Scientific Reports on 10 October 2017.
Scientific Reports 7, Article number: 12897 (2017)
Self-assembly of small biomolecules is a prevalent phenomenon that is increasingly being recognised to
hold the key to building complex structures from simple monomeric units. Small peptides, in particular
ultrashort peptides containing up to seven amino acids, for which our laboratory has found many
biomedical applications, exhibit immense potential in this regard. For next-generation applications, more intricate control is required over the self-assembly processes. We seek to find out how subtle moiety variation of peptides can affect self-assembly and nanostructure formation. To this end, we have selected a library of 54 tripeptides, derived from systematic moiety variations from seven tripeptides. Our study reveals that subtle structural changes in the tripeptides can exert profound effects on self-assembly, nanostructure formation, hydrogelation, and even phase transition of peptide nanostructures. By comparing the X-ray crystal structures of two tripeptides, acetylated leucineleucine-glutamic acid (Ac-LLE) and acetylated tyrosine-leucine-aspartic acid (Ac-YLD), we obtained valuable insights into the structural factors that can influence the formation of supramolecular peptide structures. We believe that our results have major implications on the understanding of the factors that affect peptide self-assembly. In addition, our findings can potentially assist current computational efforts to predict and design self-assembling peptide systems for diverse biomedical applications.
Figure legend: Scanning electron micrographs illustrating the four general morphologies observed with the acetylated tripeptides: (A) Amorphous structure (Ac-LVE, supernatant of 20 mg/mL; 5000×). B) Bead microstructure (Ac-LLE, solution of 20 mg/mL; 5000×). (C) Crystalline nanostructure (Ac-LVE, precipitate of 20 mg/mL; 5000×). (D) Fibrillar nanostructure (Ac-IVD, hydrogel at 20 mg/mL; 10000×). (E) Illustration of a typical set-up to assess the self-assembly and aggregation of peptides. A series of peptide concentrations (Ac-LLE-NH2 here) from 5−40 mg/mL, in steps of 5 mg/mL were prepared. This series also illustrates the four states generally observed in this study: solution (5−20 mg/mL), hydrogel (25 mg/mL; upturned vial), supernatant and precipitate (30−40 mg/mL). (F) X-ray crystal structure of Ac-LLE. Four blocks of Ac-LLE are shown and colored differently. (Left) hydrophobic interaction by the intercalating side chains of Leu1 and Leu2. (Right) hydrogen bond network. Intra- and inter-block hydrogen bonds are colored black, blue and magenta, respectively. The 2-fold axis relating the yellow and the green blocks are in green, and the 2-fold screw axis relating the yellow and the cyan blocks are in cyan.
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