Pathway dependent self-assembly of positively charged computationally designed coiled-coil peptide 'bundlemer' chains

A series of 29 amino-acids peptides were computationally designed to be self-assembled into tetrameric, anti-parallel coiled coil peptide bundles, or ‘bundlemer’, with a desired net charge. Here, peptides with +4 charge are synthesized with the N-termini of constituent peptides modified with cysteine or maleimide functionality. These two peptides are self-assembled into 2x4 nm size peptide bundlemers and subsequently conjugated by Thiol-Michael reaction to form peptide bundle chains. However, the peptides chains’ length is only controlled by stoichiometry leading to high dispersity in length. Thus, another pathway is proposed to control chain length and dispersity. Peptides are first dissolved and reacted in an organic solvent and then self-assembled with different water addition pathways, including titration and direct quenching. Transmission electron microscopy (TEM) was used to investigate the length distribution of peptide rods. Small-angle neutron scattering (SANS) was utilized to characterize the size and structure of the bundlemer chains. Polarized optical microscopy (POM) was applied to study the liquid crystalline behavior of conjugated peptide bundle chains. The effect of salt on the solution behavior of the positively charged coiled coil chains also will be discussed.