Experimental and Computational Studies Reveal an Alternative Supramolecular Structure for Fmoc-Dipeptide Self-Assembly

We have investigated the self-assembly of fluorenylmethoxycarbonyl-conjugated
dialanine (Fmoc-AA) molecules using combined computational and experimental
approaches. Fmoc-AA gels were characterized using transmission electron
microscopy (TEM), circular dichroism (CD), Fourier transform infrared
(FTIR), and wide-angle X-ray scattering (WAXS). Computationally, we
simulated the assembly of Fmoc-AA using molecular dynamics techniques.
All simulations converged to a condensed fibril structure in which
the Fmoc groups stack mostly within in the center of the fibril. However,
the Fmoc groups are partially exposed to water, creating an amphiphilic
surface, which may be responsible for the aggregation of fibrils into
nanoscale fibers observed in TEM. From the fibril models, radial distribution
calculations agree with d-spacings observed in WAXS
for the fibril diameter and π-stacking interactions. Our analyses
show that dialanine, despite its short length, adopts a mainly extended
polyproline II conformation. In contrast to previous hypotheses, these
results indicate that β-sheet-like hydrogen bonding is not prevalent.
Rather, stacking of Fmoc groups, inter-residue hydrogen bonding, and
hydrogen bonding with water play the important roles in stabilizing
the fibril structure of supramolecular assemblies of short conjugated
peptides.