De Novo Design\nand Characterization of Amphiphilic\nPeptides with Basic Side Chains for Tailored Interfacial Chemistries

Lysine–leucine (LK) peptides have been used as\nmodel systems\nand platforms for 2D material design for decades. LK peptides are\namphiphilic sequences designed to bind and fold at hydrophobic surfaces\nthrough hydrophobic leucine side chains and hydrophilic lysine side\nchains extending into the aqueous subphase. The hydrophobic periodicity\nof the sequence dictates the secondary structure at the interface.\nThis robust design makes them ideal candidates for controlling interfacial\nchemistry. This study presents the de novo design and characterization\nof two novel peptides: LRα14 and LHα14, which substitute\nlysine with arginine and histidine, respectively, in the helical LKα14\nsequence. This modification is intended to expand the LK peptide platform\nto a new basic interfacial chemistry. We explore the stability of\nthe new LRα14 and LHα14 designs with respect to changes\nin pH and salt concentration in bulk solution and at the interface\nusing circular dichroism (UV-CD) and vibrational sum-frequency generation\nspectroscopy, respectively. Notably, the structural stability of the\npeptides remains unaffected across a wide range of pH and ionic strength\nvalues. At the same time, the variation of side-chain chemistry leads\nto a wide spectrum of interfacial water structures. By extension of\nthe LK platform to include arginine and histidine, this study broadens\nthe toolbox for designing tailored interfacial chemistries with applications\nin material and biomedical sciences.