Effect of triphenylphosphonium moiety on spatial structure and biointeractions of stereochemical variants of YRFK motif.

Chemical modification of therapeutic peptides is an important approach to improving their physicochemical and pharmacokinetic properties. The triphenylphosphonium (TPP) cation has proved to be a powerful modifier; however, its effects on peptide structure and activity remain uncharacterized. In this study, cytoprotective tetrapeptides based on the YRFK opioid motif with L- or D-Arg residues were linked to (triphenylphosphonio)carboxylic acids with ethylene and pentylene spacers (TPP-3 and TPP-6 groups, respectively).