Gelation behavior of short protected peptides in organic medium

Peptide gelators have been widely explored in aqueous systems due to their prevalence in biological and medical applications. However, gelation behavior of peptides is less understood in organic medium, despite the extensive use of organic solvents in solid phase peptide synthesis, hybrid synthesis protocols, and the formation and application of organogels. Here, peptides with a short aqueous gelator sequence, lysine-tyrosine-phenylalanine or KYF, were investigated for the ability to form gels in dichloromethane (DCM) when their side groups are protected. Protected KYF-containing peptides formed gels in DCM at similar concentrations to deprotected KYF peptides in water. Structural characterization <i>via</i> Fourier transform infrared spectroscopy indicated the presence of antiparallel β-sheets in both the protected and the deprotected KYF gels. However, transmission electron microscopy and dynamic light scattering indicated the protected KYF gels in DCM consisted of short, anisotropic particles at the mesoscale, whereas the deprotected KYF gels in water showed entangled fibers. The protected KYF gels in DCM exhibited similar rheological properties to colloidal gels, namely an increasing resistance to flow at higher shear rates, a shear thinning profile, and a gel-to-fluid transition with increasing strain. Altogether, this study provides critical insights on the assembly behavior and structure of a tripeptide motif and its variants in organic medium, which can facilitate optimizing the processing conditions of similar peptides in organic solvents during synthesis or end-use applications.