The amphibian family Leptodactylidae is divided into three sub-families: Leiuperinae, Leptodactylinae, and Paratelmatobiinae. Host-defense peptides (HDPs) present in the skins of frogs belonging to the Leptodactylinae have been studied extensively, but information is limited  regarding peptides from Leiuperinae species. Peptidomic analysis of norepinephrine-stimulated skin secretions from the Tungara frog Engystomops pustulosus (Leiuperinae) collected in Trinidad led to the isolation and structural characterization of previously undescribed pustulosin-1 (FWKADVKEIG KKLAAKLAEELAKKLGEQ), [Q28E] pustulosin-1 (pustulosin-2), and pustulosin-3 (DWKETAKELLKKIGAKVAQVISDKLNPAPQ). The primary structures of these peptides do not resemble those of previously described frog skin HDPs. In addition, the secretions contained tigerinin-1EP (GCKTYLIEPPVCT) with structural similarity to the tigerinins previously identified in skin secretions from frogs from the family Dicroglossidae. Pustulosin-1 and -3 adopted extended α-helical conformations in 25% trifluoroethanol-water and in the presence of cell membrane models (sodium dodecylsulfate and dodecylphosphocholine micelles). Pustulosin-1 and -3 displayed cytotoxic activity against a range of human tumor-derived cell lines (A549, MDA-MB-231, and HT29), but their therapeutic potential for development into anti-cancer agents is limited by their comparable cytotoxic activity against non-neoplastic human umbilical vein endothelial cells. The peptides also displayed weak antimicrobial activity against Escherichia coli (MIC = 125 µM) but were inactive against Staphylococcus aureus. Tigerinin-1EP was inactive against both the tumor-derived cells and bacteria.

Peptides are remarkably interesting alternatives to several applications. In particular, antimicrobial sequences have raised major interest of the scientific community due to the resistance acquired by commonly used antibiotics. Amongst these, some dimeric peptides have shown very promising characteristics as strong biological activities and resistance against degradation by peptidases. However, despite such promising characteristics, a relatively small number of studies address dimeric peptides, mainly due to the synthesis-related obstacles in their production, whereas the well-implemented routines of solid phase peptide synthesis-which includes the possibility of automation-makes life significantly easier. Here, we present kinetic investigations of the dimerization of a cysteine-containing sequence to obtain the homodimeric antimicrobial peptide homotarsinin. Based on the structural and membrane interaction data already available for the dimer and its monomeric chain, we have proposed distinct dimerization protocols in selected environments, namely, aqueous buffer, TFE:H2O and micellar solutions. The experimental results were adjusted by a theoretical model. Both the kinetic profiles and the reaction yields are dependent on the reaction medium, clearly indicating that aggregation, peptide structure, and peptide-membrane interactions play major roles in the formation of the disulfide bond. Finally, the rationalization of the different aspects addressed here is expected to contribute to research and applications that demand the obtainment of dimeric peptides.

Cancer malignancies may broadly be described as heterogeneous disorders manifested by uncontrolled cellular growth/division and proliferation. Tumor cells utilize metabolic reprogramming to accomplish the upregulated nutritional requirements for sustaining their uncontrolled growth, proliferation, and survival. Metabolic reprogramming also called altered or dysregulated metabolism undergoes modification in normal metabolic pathways for anabolic precursor's generation that serves to continue biomass formation that sustains the growth, proliferation, and survival of carcinogenic cells under a nutrition-deprived microenvironment. A wide range of dysregulated/altered metabolic pathways encompassing different metabolic regulators have been described; however, the current review is focused to explain deeply the metabolic pathways modifications inducing upregulation of proteins/amino acids metabolism. The essential modification of various metabolic cycles with their consequent outcomes meanwhile explored promising therapeutic targets playing a pivotal role in metabolic regulation and is successfully employed for effective target-specific cancer treatment. The current review is aimed to understand the metabolic reprogramming of different proteins/amino acids involved in tumor progression along with potential therapeutic perspective elucidating targeted cancer therapy via these targets.

Guanidino compounds such as dimethylarginines (SDMA, ADMA) and L-homoarginine ((L-)hArg) can interfere with bioavailability and function of the main NO-donor L-arginine (L-Arg). High ADMA and SDMA but low L-hArg concentrations have been associated with cardio- and cerebrovascular events and mortality in adults. The role of guanidino compounds in paediatric patients remains less clear. We, therefore, compared guanidino compound levels in plasma samples of 57 individuals with chronic kidney disease (CKD) and 141 individuals without CKD from the age of 0 to 17 years, including patients with different comorbidities by correlation and regression analyses. We found highest hArg, SDMA and ADMA concentrations in neonates (Kruskal-Wallis, p < 0.001 for all). From the age of 1 year on, hArg levels increased, whereas SDMA und ADMA levels further decreased in children. SDMA and ADMA are higher in children with CKD independent of GFR (mean factor 1.92 and 1.38, respectively, p < 0.001 for both), and SDMA is strongly correlated with creatinine concentration in children with CKD (Spearman's rho 0.74, p < 0.001). We provide guanidino compound levels in a large sample covering all paediatric age groups for the first time. Our data can be used to assess the role of guanidino compounds such as hArg in disease states, i.e. cerebro- and cardiovascular disorders in childhood and adolescence.

To describe the association between levels of homocitrulline (HCit) and the degree of albumin carbamylation in a cohort of hemodialyzed patients. Plasma total and protein-bound HCit concentrations in samples from hemodialyzed patients included in NICOREN trial were determined by LC-MS/MS at baseline and after 24 weeks of treatment with either sevelamer or nicotinamide. HCit concentrations at all timepoints and in both groups were positively and significantly correlated with the degree of albumin carbamylation. Plasma concentrations of total HCit, protein-bound HCit and carbamylated albumin did not decrease after 24 weeks of treatment with either sevelamer or nicotinamide. The present results demonstrate that plasma total and protein-bound HCit concentrations were closely associated with albumin carbamylation in hemodialyzed patients. Therefore, total and protein-bound HCit concentrations might be valuable biomarkers of the overall intensity of protein carbamylation in this context. Given the less complex and time-consuming analytical methods required, these markers should be favored in future clinical studies of carbamylation reaction.

Gut-derived neuroactive metabolites from amino acids perform a broad range of physiological roles in the body. However, the interaction between microbiota and epithelium in the metabolism of amino acids with neuroactive properties remains unclear in the colon of piglets. To investigate the microbial and epithelial metabolism, metagenomics and mucosal metabolomics were performed using colonic samples from 12 ileum-canulated piglets subjected to a 25-day infusion with saline or antibiotics. We categorized 23 metabolites derived from the metabolism of tryptophan, glutamate, and tyrosine, known as precursors of neuroactive metabolites. Microbial enzymes involved in the kynurenine synthesis via arylformamidase, 4-aminobutyric acid (GABA) synthesis via putrescine aminotransferase, and tyramine synthesis via tyrosine decarboxylase were identified in Clostridiales bacterium, uncultured Blautia sp., and Methanobrevibacter wolinii, respectively. Antibiotics significantly affected the microbiota involved in tryptophan-kynurenine and glutamate-GABA metabolism. An increase in the relative abundance of putrescine aminotransferase and Blautia sp. correlated positively with an increase in luminal GABA concentration. Overall, our findings provide new insights into the microbial ability to metabolize key amino acids that are precursors of neuroactive metabolites.

Amino acids are essential for the survival of all living organisms and living cells. Amino acid transporters mediate the transport and absorption of amino acids, and the dysfunction of these proteins can induce human diseases. Cationic amino acid transporters (CAT family, SLC7A1-4, and SLC7A14) are considered to be a group of transmembrane transporters, of which SLC7A1-3 are essential for arginine transport in mammals. Numerous studies have shown that CAT family-mediated arginine transport is involved in signal crosstalk between malignant tumor cells and immune cells, especially T cells. The modulation of extracellular arginine concentration has entered a number of clinical trials and achieved certain therapeutic effects. Here, we review the role of CAT family on tumor cells and immune infiltrating cells in malignant tumors and explore the therapeutic strategies to interfere with extracellular arginine concentration, to elaborate its application prospects. CAT family members may be used as biomarkers for certain cancer entities and might be included in new ideas for immunotherapy of malignant tumors.