Understanding the intermediates or transition states in organic reactions has made it possible to develop theories and to synthesize important compounds. In contrast to organic reaction intermediates and even protein folding intermediates, the intermediates of peptide/protein self-assembly are not very well understood. Here we report that the self-assembly kinetics of linear heterochiral peptides are significantly slower than those of the corresponding homochiral peptides, which enables direct microscopic observation of assembly intermediates. By designing racemic or asymmetric heterochiral peptides, we were able to discover unusual mixed helical (MP-helix) and overtwisted intermediates. The convergence of equilibrium morphology between the homochiral and heterochiral peptides enables us to reasonably deduce the unobservable intermediates of rapidly assembling homochiral peptides. By utilizing the discovered information about the assembly intermediates, we were able to develop a functional NMR alignment medium that enables the measurement of residual dipolar couplings (RDCs) in a time-dependent manner. Although much less studied than their cyclic counterparts, the linear form of heterochiral peptides provides a means of obtaining a more in-depth understanding of the self-assembly pathway and of developing sophisticated bottom-up materials.
Bibliographical noteFunding Information:
This work was supported by grants from the National Research Foundation (NRF) of Korea (2017R1A2A2A05069773). We thank Pohang Accelerator Laboratory (PAL) for WAXS experiments. We gratefully acknowledge Dr. Eunjung Bang in Korea Basic Science Institute (KBSI) Western Seoul Center for assistance with the 2 H NMR experiments.
© 2020 American Chemical Society.
All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Physics and Astronomy(all)