WITHDRAWN: Photobuforin II, a fluorescent photoswitchable peptide.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.bbadva.2023.100106. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Photobuforin II, a fluorescent photoswitchable peptide.

Antimicrobial peptide buforin II translocates across the cell membrane and binds to DNA. Its sequence is identical to a portion of core histone protein H2A making it a highly charged peptide. Buforin II has a proline residue in the middle of its sequence that creates a helix-hinge-helix motif which has been found to play a key role in its ability to translocate across the cell membrane. To explore the structure-function relationship of this proline residue this study has replaced P11 with a meta-substituted azobenzene amino acid (Z). The resultant peptide, photobuforin II, retained the secondary structure and membrane activity of the naturally occurring peptide while gaining new spectroscopic properties. Photobuforin II can be isomerized from its trans to cis isomer upon irradiation with ultra-violet (UV) light and from its cis to trans isomer upon irradiation with visible (VL). Photobuforin II is also fluorescent with an emission peak at 390 nm. The intrinsic fluorescence of the peptide was used to determine binding to the membrane and to DNA. VL-treated photobuforin II has a 2-fold lower binding constant compared to UV-treated photobuforin and causes 11-fold more membrane leakage in 3:1 POPC:POPG vesicles. Photobuforin II provides insights into the importance of structure function relationships in membrane active peptides while also demonstrating that azobenzene can be used in certain peptide sequences to produce intrinsic fluorescence.

Substituting azobenzene for proline in melittin to create photomelittin: A light-controlled membrane active peptide.

In this article we present the synthesis and characterization of a new form of the membrane active peptide melittin: photomelittin. This peptide was created by substituting the proline residue in melittin for a synthetic azobenzene amino acid derivative. This azobenzene altered the membrane activity of the peptide while retaining much of the secondary structure. Furthermore, the peptide demonstrates added light-dependent activity in leakage assays. There is a 1.5-fold increase in activity when exposed to UV light as opposed to visible light. The peptides further exhibit light-dependent hemolytic activity against human red blood cells. This will enable future studies optimizing photomelittin and other azobenzene-containing membrane active peptides for uses in medicine, drug delivery, and other biotechnological applications.

Applications and evolution of melittin, the quintessential membrane active peptide.

Melittin, the main venom component of the European Honeybee, is a cationic linear peptide-amide of 26 amino acid residues with the sequence: GIGAVLKVLTTGLPALISWIKRKRQQ-NH2. Melittin binds to lipid bilayer membranes, folds into amphipathic α-helical secondary structure and disrupts the permeability barrier. Since melittin was first described, a remarkable array of activities and potential applications in biology and medicine have been described. Melittin is also a favorite model system for biophysicists to study the structure, folding and function of peptides and proteins in membranes. Melittin has also been used as a template for the evolution of new activities in membranes. Here we overview the rich history of scientific research into the many activities of melittin and outline exciting future applications.

Synergies with and Resistance to Membrane-Active Peptides.

Membrane-active peptides (MAPs) have long been thought of as the key to defeating antimicrobial-resistant microorganisms. Such peptides, however, may not be sufficient alone. In this review, we seek to highlight some of the common pathways for resistance, as well as some avenues for potential synergy. This discussion takes place considering resistance, and/or synergy in the extracellular space, at the membrane, and during interaction, and/or removal. Overall, this review shows that researchers require improved definitions of resistance and a more thorough understanding of MAP-resistance mechanisms. The solution to combating resistance may ultimately come from an understanding of how to harness the power of synergistic drug combinations.