Exciton Coupling of Phenylalanine Reveals Conformational Changes of Cationic Peptides

Abstract

AbstractCircular dichroism (CD) is a versatile tool to investigate the secondary structure of proteins. Conventionally, CD signals in the far‐UV region are primarily attributed to peptide bond absorption; likewise aromatic residue analysis has typically only focussed on the near‐UV absorption characteristics. However, crucial information that is contained in electronic transitions occurring in the far‐UV has not been fully exploited to date, despite the significant potential offered by such measurements to yield a window into protein structure and self‐assembly under native conditions. In this work, we strive towards a quantitative interpretation of CD spectra by detailing the contributions of aromatic chromophores in the far‐UV and accurately describing unfolded states of charged amino acid side chains. To this end, we probe conformational changes of cationic peptides, which impact on their antimicrobial activity, as a function of pH and we show that the emerging far‐UV signatures yield information on phenylalanine exciton coupling. This work thus furthers our understanding of the folding mechanisms of cationic peptides, which are considered to be molecules of key interest in the context of overcoming antimicrobial resistance.