Abstract
We previously used an orthogonal high-throughput screen to select peptides that spontaneously cross synthetic lipid bilayers without permeabilization. Interestingly, many of the 12-residue spontaneous membrane translocating peptides (SMTPs) selected from the library contained a consensus LRLLR motif. We hypothesized that the conserved LRLLR motif could be a minimal motif for spontaneous membrane translocation. To test this and to explore the mechanism of spontaneous membrane translocation, we synthesized six arginine spacing variants of LRLLR and compared their membrane partitioning, translocation, and perturbation to one of the parent SMTPs, called TP2.
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