Transmembrane β‐peptide helices as molecular rulers at the membrane surface

Abstract

β-Peptides are known to form 14-helices with high conformational rigidity, helical persistence length, and well-defined spacing and orientation regularity of amino acid side chains. Therefore, β-peptides are well suited to serve as backbone structures for molecular rulers. On the one hand, they can be functionalized in a site-specific manner with molecular probes or fluorophores, and on the other hand, the β-peptide helices can be recognized and anchored in a biological environment of interest. In this study, the β-peptide helices were anchored in lipid bilayer membranes, and the helices were elongated in the outer membrane environment. The distances of the covalently bound probes to the membrane surface were determined using grapheneinduced energy transfer (GIET) spectroscopy, a method based on the distancedependent quenching of a fluorescent molecule by a nearby single graphene sheet. As a proof of principle, the predicted distances were determined for two fluorophores bound to the membrane-anchored β-peptide molecular ruler.

Artificial peptides to induce membrane denaturation and disruption and modulate membrane composition and fusion

“…Subsequently, GIET spectroscopy analyses were performed in order to evaluate the distance of the dye from the lipid surface. Potential application for structures like these is the positioning of probes at given distances from the plasma membrane, in order to measure the ion concentration in its proximity 221 …”

“…Potential application for structures like these is the positioning of probes at given distances from the plasma membrane, in order to measure the ion concentration in its proximity. 221 Analogously to conventional α-CPPs, β-peptides and α/β-hybrids have also shown the ability to permeate the plasma membrane following both direct penetration and endocytosis. 222,223 Moreover, the resistance of β-peptides toward degradation by proteases made them promising candidates for the development of antimicrobic peptides.…”