||Effective modification of cell death-inducing intracellular peptides by means of a photo-cleavable peptide array-based screening system
Ikko, Kozaki ,
Kazunori, ShimizuHiroyuki, Honda
Journal of Bioscience and Bioengineering
214 , 2017-08 , Elsevier
Intracellular functional peptides that play a significant role inside cells have been receiving a lot of attention asregulators of cellular activity. Previously, we proposed a novel screening system for intracellular functional peptides; itcombined a photo-cleavable peptide array system with cell-penetrating peptides (CPPs). Various peptides can bedelivered into cells and intracellular functions of the peptides can be assayed by means of our system. The aim of thepresent study was to demonstrate that the proposed screening system can be used for assessing the intracellular activityof peptides. The cell death-inducing peptide (LNLISKLF) identified in a mitochondria-targeting domain (MTD) of theNoxa protein served as an original peptide sequence for screening of peptides with higher activity via modification ofthe peptide sequence. We obtained 4 peptides with higher activity, in which we substituted serine (S) at the fifth positionwith phenylalanine (F), valine (V), tryptophan (W), or tyrosine (Y). During analysis of the mechanism of action, themodified peptides induced an increase in intracellular calcium concentration, which was caused by the treatment withthe original peptide. Higher capacity for cell death induction by the modified peptides may be caused by increasedhydrophobicity or an increased number of aromatic residues. Thus, the present work suggests that the intracellularactivity of peptides can be assessed using the proposed screening system. It could be used for identifying intracellularfunctional peptides with higher activity through comprehensive screening.