The pH sensitivity of histidine-containing lytic peptides.
Many bioactive peptides are featured by their unique amino acid compositions such as argine/lysine-rich peptides. However, histidine-rich bioactive peptides are hardly found. In this study, histidine-containing peptides were constructed by selectively replacing the corresponded lysine residues in a lytic peptide LL-1 with histidines. Interestingly, all resulting peptides demonstrated pH-dependent activities. The cell lysis activities of these peptides could be increased up to four times as the solution pHs dropped from pH = 7.4 to pH = 5.5. The pH sensitivity of a histidine-containing peptide was determined by histidine substitution numbers. Peptide derivatives with more histidines were associated with increased pH sensitivity. Results showed that not the secondary structures but pH-affected cell affinity changes were responsible for the pH-dependent activities of histidine-containing peptides. The histidine substitution approach demonstrated here may present a general strategy to construct bioactive peptides with desired pH sensitivity for various applications.
Tu
Zhigang
Z
Department of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, USA.
Young
Albert
A
Murphy
Christopher
C
Liang
Jun F
JF
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D010455:Peptides; D006639:Histidine; D008239:Lysine