While peptide gelation in aqueous environments has been extensively explored for biomedical applications, peptide gelation behavior in organic medium is not well understood, despite the widespread use of organic solvents in solid phase peptide synthesis, hybrid synthesis protocols, and organogel applications. Here, we investigated the gelation behavior of a short peptide sequence, lysine-tyrosine-phenylalanine or KYF, with protected side chains and its derivatives in dichloromethane (DCM). Protected KYF peptides gelled in DCM at 40 mM, whereas deprotected peptides formed gels in water at the same concentration. Structural characterization via 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 peptide gels consist of short, anisotropic particles at the mesoscale, whereas the deprotected peptide gels in water form entangled fibers. The rheology of protected peptide gels in DCM show an increasing resistance to flow at higher shear rates, a shear thinning profile, and a gel-to-sol transition with increasing strain. Future work will explore the effects of length, sequence, structure and residue positions of the protected peptides on gelation. 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 peptides in organic solvents during synthesis, as well as provide guidelines for designing organogels for wide range of applications.
