1.C.82 The Pore-forming Amphipathic Helical Peptide HP(2-20) (HP2-20) Family
HP(2-20) (residues 2-20 of parental HP derived from the N-terminus of Helicobacter pylori Ribosomal Protein L1) and its analogue, HPA3, exhibit broad-spectrum antimicrobial activity. Analogues, HPA3 and HPA3NT3, exert potent antibacterial effects in low-salt buffer and antifungal activity against chitin-containing fungi, while having little or no hemolytic activity or cytotoxicity against mammalian cell lines. HP(2-20) and its analogues interact with liposomes and disturb both neutral and negatively-charged membranes, as demonstrated by the release of encapsulated fluorescent markers (Park et al., 2007). The pore created by HP(2-20) shows that the radius is approximately 1.8 nm, whereas HPA3, HPA3NT3, and melittin have apparent radii between 3.3 and 4.8 nm. Electron microscopy showed that liposomes and various microbial cells treated with HPA3 and HPA3NT3 exhibited oligomerization and blebbing similar to that seen with melittin, while HP(2-20) exhibited flabbiness. Thus, HP(2-20) may exert its antibiotic effects through a small pore (about 1.8 nm), whereas HPA3 and HPA3NT3 formed larger pores. HPA3 pore formation is electrophoretically facilitated by trans-negative transmembrane potentials, and HPA3 peptides translocate into the trans monolayers after forming the pores (Merenta et al., 2008).
The transport reaction catalyzed by HP(2-20) and its analogues is:
small molecule (in) small molecule (out).