Constructing bioactive peptides with pH-dependent activities.
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.
Tu
Zhigang
Z
Department of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
Volk
Melanie
M
Shah
Khushali
K
Clerkin
Kevin
K
Liang
Jun F
JF
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
D005452:Fluoresceins; D008823:Micelles; D010455:Peptides; D006639:Histidine; D001120:Arginine; D008239:Lysine; C007740:fluorexon