phase synthesis was used to produce 5 hybrid peptides containing sequences from the antibacterial peptide, cecropin A, and from the bee venom toxin, melittin. Four of these chimeric peptides showed good antibacterial activity against representative Gram-negative and Gram-positive bacterial species. The best hybrid, cecropin A(l-13)-melittin(l-13) was IOO-fold more active than cecropin A against Staphylococcus uureus. It was also a lo-fold better antimalarial agent than cecropin B or magainin 2. Sheep red cells were lysed by melittin at low concentrations, but not by the hybrid molecules, even at 50 times higher concentrations. Cecropin A; Melittin; (Staphylococcus aureus, Plasmodium falciparium)

and antimalarial properties of peptides that are cecropin-melittin hybrids

Bacterial infections caused by 'superbugs' are increasing globally, and conventional antibiotics are becoming less effective against these bacteria, such that we risk entering a post-antibiotic era. In recent years, antimicrobial peptides (AMPs) have gained significant attention for their clinical potential as a new class of antibiotics to combat antimicrobial resistance. In this review, we discuss several facets of AMPs including their diversity, physicochemical properties, mechanisms of action, and effects of environmental factors on these features. This review outlines various chemical synthetic strategies that have been applied to develop novel AMPs, including chemical modifications of existing peptides, semi-synthesis, and computer-aided design. We will also highlight novel AMP structures, including hybrids, antimicrobial dendrimers and polypeptides, peptidomimetics, and AMP-drug conjugates and consider recent developments in their chemical synthesis.

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The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions.

A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes.

Antimicrobial peptides conjugated with fatty acids on the side chain of D-amino acid promises antimicrobial potency against multidrug-resistant bacteria

Background The rapid increase of drug resistance in conventional antibiotics promotes the discovery and development of antimicrobial peptides (AMPs), which are important components of natural immunity. Due to the specific action modes targeting for cell membrane, AMPs have become a promising substance for bacterium inhibitions barely with no drug resistance. Here we reviewed the structure characteristics related with bactericide actions, including peptides constituents, molecular length, molecular charges and so on. And we also summarized the common mode of actions of AMPs raised by researchers. The structure-mechanism relationship was discussed. The commonly used methods for mechanism study were also listed. Key findings and conclusions The structures of AMPs were strongly related with its efficacy, such as constituents, molecular length, charges, secondary structures. The main mechanisms of AMPs were divided into membrane targets and intracellular targets. Some advanced and new techniques were applied in the mechanism study. Most of the existed mechanisms are still suppositional, and techniques were mainly focused on membrane-associated mechanism, only few of them were related with intracellular factors. Therefore, more new methods are expected to explore the authentic mechanisms and better results as well as more intracellular targets. This review provides a reference for future AMPs chemical modification and mechanism exploration.

The structure-mechanism relationship and mode of actions of antimicrobial peptides: A review

Hybrid peptides integrating different functional domains of peptides have many advantages, such as remarkable antimicrobial activity, lower hemolysis and ideal cell selectivity, compared with natural antimicrobial peptides. FV7 (FRIRVRV-NH2), a consensus amphiphilic sequence was identified as being analogous to host defense peptides. In this study, we designed a series of hybrid peptides FV7-LL-37 (17–29) (FV-LL), FV7-magainin 2 (9–21) (FV-MA) and FV7-cecropin A (1–8) (FV-CE) by combining the FV7 sequence with the small functional sequences LL-37 (17–29) (LL), magainin 2 (9–21) (MA) and cecropin A (1–8) (CE) which all come from well-described natural peptides. The results demonstrated that the synthetic hybrid peptides, in particular FV-LL, had potent antibacterial activities over a wide range of Gram-negative and Gram-positive bacteria with lower hemolytic activity than other peptides. Furthermore, fluorescent spectroscopy indicated that the hybrid peptide FV-LL exhibited marked membrane destruction by inducing outer and inner bacterial membrane permeabilization, while scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that FV-LL damaged membrane integrity by disrupting the bacterial membrane. Inhibiting biofilm formation assays also showed that FV-LL had similar anti-biofilm activity compared with the functional peptide sequence FV7. Synthetic cationic hybrid peptides based on FV7 could provide new models for combining different functional domains and demonstrate effective avenues to screen for novel antimicrobial agents.

High Specific Selectivity and Membrane-Active Mechanism of Synthetic Cationic Hybrid Antimicrobial Peptides Based on the Peptide FV7.

Antimicrobial peptides (AMPs) offer great hope and a promising opportunity to overcome the rapid development of drug-resistant pathogenic microbes. However, AMPs often lack the stability required for a successful systemic drug. Hybridizing different AMPs is a simple and effective strategy to obtain novel peptides. N-terminal fragment of cecropin A (CA (1-8)) is often used to hybridize with other AMPs to reduce cytotoxicity. However, hybridizing with CA (1-8) in improving the stability of AMPs is not clear. Therefore, a series of peptides were designed by combining with CA (1-8) and their antibacterial activity and stability in the presence of salts and human serum were evaluated. The resultant α-helical hybrid peptide CA-FO composed of CA (1-8) and the most potent region of Fowlicidin-2 (FO (1-15)) exhibited excellent antibacterial activity (2-8 μM) and cell selectivity toward bacterial over mammalian cells. Moreover, CA-FO still retained vigorous antimicrobial activity in the presence of human serum and salts at physiological concentrations. CA-FO exhibited effective antibacterial activity by increasing membrane permeability and damaging membrane integrity. In conclusion, these results indicated the success of hybridization in designing and optimizing AMPs with improved stability and selectivity and the peptide CA-FO can be further evaluated as peptide-therapy to treat bacterial infections.

Di Wu

Papers

High Specific Selectivity and Membrane-Active Mechanism of Synthetic Cationic Hybrid Antimicrobial Peptides Based on the Peptide FV7.

Hybridization with Insect Cecropin A (1-8) Improve the Stability and Selectivity of Naturally Occurring Peptides.