title: Constructing bioactive peptides with pH-dependent activities.
abstract: Many bioactive peptides are featured by their arginine and lysine rich contents. In this study, lysine and arginine residues in lytic peptides were selectively replaced by histidines. Although resulting histidine-containing lytic peptides had decreased activity, they did show pH-dependent cytotoxicity. The activity of the constructed histidine-containing lytic peptides increased 2-8 times as the solution pH changed from 7.4 to 5.5. More importantly, these histidine-containing peptides maintain the same cell killing mechanism as their parent peptides by causing cell lysis. Both the activity and pH-sensitivity of histidine-containing peptides are tunable by adjusting histidine substitution numbers and positions. This study has presented a general strategy to create bioactive peptides with desired pH-sensitivity to meet the needs of various applications such as cancer treatments.
authors.affiliation: Department of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tu
authors.forename: Melanie
authors.initials: M
authors.lastname: Volk
authors.forename: Khushali
authors.initials: K
authors.lastname: Shah
authors.forename: Kevin
authors.initials: K
authors.lastname: Clerkin
authors.forename: Jun F
authors.initials: JF
authors.lastname: Liang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D016923:Cell Death; D002460:Cell Line; D005452:Fluoresceins / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D009369:Neoplasms; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014184:Transplantation, Homologous
chemical_list: D005452:Fluoresceins; D008823:Micelles; D010455:Peptides; D006639:Histidine; D001120:Arginine; D008239:Lysine; C007740:fluorexon