The Odilorhabdin Antibiotic Biosynthetic Cluster and Acetyltransferase Self-Resistance Locus Are Niche and Species Specific

Odilorhabdins (ODLs) constitute a novel antibiotic family with promising properties for treating problematic multidrug-resistant Gram-negative bacterial infections. ODLs are 10-mer linear cationic peptides inhibiting bacterial translation by binding to the small subunit of the ribosome.

Peptide-Mucin Binding and Biosimilar Mucus-Permeating Properties

This study aimed to understand the role of the mucus layer (a biological hydrogel) in the transport mechanisms of peptides. Using established in vitro models, the mucin-binding activity and mucus-permeating property of peptides were determined. Uncharged peptides with relatively high hydrophilicity, including MANT, TNGQ, and PASL, as well as cationic peptides, including KIPAVF and KMPV, possessed strong mucin-binding activity. Contrarily, uncharged peptides with high hydrophobicity index, including YMSV and QIGLF, exhibited weak mucin-binding activity. Only TNGQ, which has high Boman index and hydrophilicity, showed a high biosimilar mucus-permeating property with a permeability of 96 ± 30% after 60 min. TNGQ showed the potential for high bioavailability due to the high mucin-binding and biosimilar mucus-permeating activities.

Bioactive cationic peptides as potential agents for breast cancer treatment

Breast cancer continues to affect millions of women worldwide, and the number of new cases dramatically increases every year. The physiological causes behind the disease are still not fully understood. One in every 100 cases can occur in men, and although the frequency is lower than among women, men tend to have a worse prognosis of the disease. Various therapeutic alternatives to combat the disease are available. These depend on the type and progress of the disease, and include chemotherapy, radiotherapy, surgery, and cancer immunotherapy. However, there are several well-reported side effects of these treatments that have a significant impact on life quality, and patients either relapse or are refractory to treatment. This makes it necessary to develop new therapeutic strategies. One promising initiative are bioactive peptides, which have emerged in recent years as a family of compounds with an enormous number of clinical applications due to their broad spectrum of activity. They are widely distributed in several organisms as part of their immune system. The antitumoral activity of these peptides lies in a nonspecific mechanism of action associated with their interaction with cancer cell membranes, inducing, through several routes, bilayer destabilization and cell death. This review provides an overview of the literature on the evaluation of cationic peptides as potential agents against breast cancer under different study phases. First, physicochemical characteristics such as the primary structure and charge are presented. Secondly, information about dosage, the experimental model used, and the mechanism of action proposed for the peptides are discussed.

Bioactive Cationic Peptides as Potential Agents for Breast Cancer Treatment

Breast cancer continues to affect millions of women worldwide, and the number of new cases dramatically increases every year. The physiological causes behind the disease are still not fully understood. One in every 100 cases can occur in men, and although the frequency is lower than among women, men tend to have a worse prognosis of the disease. Various therapeutic alternatives to combat the disease are available. These depend on the type and progress of the disease, and include chemotherapy, radiotherapy, surgery, and cancer immunotherapy. However, there are several well-reported side effects of these treatments that have a significant impact on life quality, and patients either relapse or are refractory to treatment. This makes it necessary to develop new therapeutic strategies. One promising initiative are bioactive peptides, which have emerged in recent years as a family of compounds with an enormous number of clinical applications due to their broad spectrum of activity. They are widely distributed in several organisms as part of their immune system. The antitumoral activity of these peptides lies in a nonspecific mechanism of action associated with their interaction with cancer cell membranes, inducing, through several routes, bilayer destabilization and cell death. This review provides an overview of the literature on the evaluation of cationic peptides as potential agents against breast cancer under different study phases. First, physicochemical characteristics such as the primary structure and charge are presented. Secondly, information about dosage, the experimental model used, and the mechanism of action proposed for the peptides are discussed.

Cationic Peptides and their Cu(II) and Ni(II) Complexes: Coordination and Biological Characteristics

Antimicrobial peptides are a promising group of compounds used for the treatment of infections. In some cases, metal ions are essential to activate these molecules. Examples of metalloantibiotics are, for instance, bleomycin and dermcidin. This study is focused on three new pseudopeptides with potential biological activity. The coordination behavior of all ligands with Cu(II) and Ni(II) ions has been examined. Various analytical methods such as potentiometric titration, UV-Vis and CD spectroscopies, and mass spectrometry were used. All compounds are convenient chelators for metal ion-binding. Two of the ligands tested have histidine residues. Surprisingly, imidazole nitrogen is not involved in the coordination of the metal ion. The N-terminal amino group, Dab side chains, and amide nitrogen atoms of the peptide bonds coordinated Cu(II) and Ni(II) in all the complexes formed. The cytotoxicity of three pseudopeptides and their complexes was evaluated. Moreover, their other model allowed for assessing the attenuation of LPS-induced cytotoxicity and anti-inflammatory activities were also evaluated, the results of which revealed to be very promising.

Cationic Clitoria ternatea Seed Peptide as a Potential Novel Bioactive Molecule

Background: While several biologics have been reported from different parts of Clitoria ternatea, a herbaceous climber of the family Fabaceae, specific production of cationic peptides other than cyclotides (<3.7 kDa) has barely been investigated or their bioactive potential looked into. Objective: To uncover potential bioactivities and characteristics of novel cationic peptides from C. ternatea seeds. Methods: C. ternatea seed cationic peptide purified by simple and cost-effective procedures was analyzed by electrophoresis and mass spectrometry. Antimicrobial efficacy was evaluated against bacterial and fungal pathogens. Antioxidant potential was quantified by in vitro antioxidant assays. Physicochemical characterization and Tandem mass spectrometry were performed. Results: An 8.5 kDa cationic peptide purified from C. ternatea seeds was active against Candida albicans, Staphylococcus aureus, Aeromonas hydrophila and Escherichia coli at a minimum inhibitory concentration in the range of 8-32 μg/ml. This activity was totally uncompromised at pH 5-8 or after 1 h of heat treatment at 70-80 ºC, but was sensitive to protease treatment. Concentration-dependent free-radical scavenging activity and ferric-reducing capacity demonstrated the antioxidant potential of the peptide. Tandem MS analysis of trypsin-digested peptide based on shotgun proteomics detected matching peptide sequences with one or two cysteine residues but had low sequence coverage (≤17%) to known sequences in the C. ternatea protein database. Taken together, the distinct characteristics of this novel 8.5 kDa peptide clearly distinguishes it from known cyclotides of C. ternatea. Conclusions: Insights have been obtained into the functional characteristics of what appears to be a novel cationic peptide from C. ternatea seeds, exhibiting significant antimicrobial and antioxidant activities.

Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma

The study investigates the antitumor effect of two cationic peptides, R-DIM-P-LF11-215 (RDP215) and the D-amino acid variant 9D-R-DIM-P-LF11-215 (9D-RDP215), targeting the negatively charged lipid phosphatidylserine (PS) exposed by cancer cells, such as of melanoma and glioblastoma. Model studies mimicking cancer and non-cancer membranes revealed the specificity for the cancer-mimic PS by both peptides with a slightly stronger impact by the D-peptide. Accordingly, membrane effects studied by DSC, leakage and quenching experiments were solely induced by the peptides when the cancer mimic PS was present. Circular dichroism revealed a sole increase in β-sheet conformation in the presence of the cancer mimic for both peptides; only 9D-RDP215 showed increased structure already in the buffer. Ex vitro stability studies by SDS-PAGE as well as in vitro with melanoma A375 revealed a stabilizing effect of D-amino acids in the presence of serum, which was also confirmed in 2D and 3D in vitro experiments on glioblastoma LN-229. 9D-RDP215 was additionally able to pass a BBB model, whereupon it induced significant levels of cell death in LN-229 spheroids. Summarized, the study encourages the introduction of D-amino acids in the design of antitumor peptides for the improvement of their stable antitumor activity.