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.
Department of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, USA.
Zhigang
Z
Tu
Albert
A
Young
Christopher
C
Murphy
Jun F
JF
Liang
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