Hydrogelation and self-assembly of Fmoc-tripeptides: unexpected influence of sequence on self-assembled fibril structure, and hydrogel modulus and anisotropy.
The self-assembly and hydrogelation properties of two Fmoc-tripeptides [Fmoc = N-(fluorenyl-9-methoxycarbonyl)] are investigated, in borate buffer and other basic solutions. A remarkable difference in self-assembly properties is observed comparing Fmoc-VLK(Boc) with Fmoc-K(Boc)LV, both containing K protected by N(epsilon)-tert-butyloxycarbonate (Boc). In borate buffer, the former peptide forms highly anisotropic fibrils which show local alignment, and the hydrogels show flow-aligning properties. In contrast, Fmoc-K(Boc)LV forms highly branched fibrils that produce isotropic hydrogels with a much higher modulus (G' > 10(4) Pa), and lower concentration for hydrogel formation. The distinct self-assembled structures are ascribed to conformational differences, as revealed by secondary structure probes (CD, FTIR, Raman spectroscopy) and X-ray diffraction. Fmoc-VLK(Boc) forms well-defined beta-sheets with a cross-beta X-ray diffraction pattern, whereas Fmoc-KLV(Boc) forms unoriented assemblies with multiple stacked sheets. Interchange of the K and V residues when inverting the tripeptide sequence thus leads to substantial differences in self-assembled structures, suggesting a promising approach to control hydrogel properties.
Cheng
G
G
Department of Chemistry, University of Reading, Reading RG6 6AD, United Kingdom.
Castelletto
V
V
Moulton
C M
CM
Newby
G E
GE
Hamley
I W
IW
D016880:Anisotropy; D002942:Circular Dichroism; D020285:Cryoelectron Microscopy; D005449:Fluorenes / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007930:Leucine / Q000031:analogs & derivatives / Q000737:chemistry; D008853:Microscopy; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D014633:Valine / Q000737:chemistry; D014961:X-Ray Diffraction
D005449:Fluorenes; D010455:Peptides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C082231:N-(fluorenyl-9-methoxycarbonyl)leucine; D007930:Leucine; D014633:Valine