Regulation of Antimicrobial Peptide Activity via Tuning Deformation Fields by Membrane-Deforming Inclusions

Antimicrobial peptides (AMPs) are considered prospective antibiotics. Some AMPs fight bacteria via cooperative formation of pores in their plasma membranes. Most AMPs at their working concentrations can induce lysis of eukaryotic cells as well. Gramicidin A (gA) is a peptide, the transmembrane dimers of which form cation-selective channels in membranes. It is highly toxic for mammalians as being majorly hydrophobic gA incorporates and induces leakage of both bacterial and eukaryotic cell membranes. Both pore-forming AMPs and gA deform the membrane. Here we suggest a possible way to reduce the working concentrations of AMPs at the expense of application of highly-selective amplifiers of AMP activity in target membranes. The amplifiers should alter the deformation fields in the membrane in a way favoring the membrane-permeabilizing states. We developed the statistical model that allows describing the effect of membrane-deforming inclusions on the equilibrium between AMP monomers and cooperative membrane-permeabilizing structures. On the example of gA monomer-dimer equilibrium, the model predicts that amphipathic peptides and short transmembrane peptides playing the role of the membrane-deforming inclusions, even in low concentration can substantially increase the lifetime and average number of gA channels.

Top-down and Bottom-up Approaches Revealed New Categories of Peptides from the Venom of Moroccan Scorpion Androctonus mauretanicus

Background: Androctonus mauretanicus (Am) is one of the most hazardous scorpions in Morocco and has a highly toxic venom responsible for severe cases of envenomation. However, few studies have focused on decifering its proteic composition. Objectives: Herein, we aim to map out the complete proteome of the Am venom in order to highlight its complexity and the polymorphism of its toxic content. This, in turn, will lead to a deeper understanding of the toxins’ mechanism of action and will help uncover those with therapeutic potential. Methods: Top-down and bottom-up proteomic approaches were used complementarily to decipher the proteome of the Am venom. These approaches were carried out on nano-high liquid chromatography coupled to nano-electrospray tandem mass spectrometry (Nano-LC-ESI-MS/MS). Results: Am venom encloses a complex mixture of 269 different compounds with molecular weights ranging from 1618.74 to 14 214.84 Da. The most abundant ones showed masses from 6185.92 to 7899.53 Da (53.89%) followed by those ranging from 2079.25 to 5969.63 Da (37.81%). Interestingly, the combination of the results of both approaches allowed the screening of a total of 112 peptides. The highest percentage was represented by neuropeptides (87%), including NaTxs, KTxs, ClTxs, venom proteins, venom neuropeptides, and myotropic neuropeptides. Moreover, other peptides were identified, such as antimicrobial peptides, amphipathic peptides, cysteine-rich venom peptides, enzymes, kunitz-type inhibitor and orphan peptides. Conclusion: The Am venom appears to contain a great amount of diverse peptides, some of which could prospectively be exploited for their pharmaceutical potential.

Sequence-Selective Recognition of Cationic Amphipathic Tripeptides with Similar Structures in Aqueous Solution by Cucurbit[7]uril

The sequence-selective recognition of cationic amphipathic peptides by synthetic receptors is significant to biological applications, but it is still a great challenge. Here we firstly study the binding characteristics of...