Piscidins, antimicrobial peptides isolated from fish, are potent against a variety of human pathogens; they show minimum inhibitory concentration values comparable to those of commercially used antimicrobials. Piscidins 1 and 2 are generally more effective than piscidin 3 when applied alone; the contrary is observed for their metal complexes: Zn(II) and Cu(II) coordination does not enhance the efficacy of piscidins 1 and 2, while a moderate enhancement is observed for piscidin 3. All three piscidins bind Cu(II) in a so-called albumin-like binding mode, while for Zn(II) complexes, two coordination modes are observed: piscidins 1 and 2 bind Zn(II) by imidazole nitrogens from His4, His11, and His17 side chains; piscidin 3 coordinates Zn(II) by His3, His4, and His11 imidazole nitrogens and additionally supports the interaction, formed by carbonyl oxygen from His4.
View Article and Find Full Text PDFElectrospray ionization mass spectrometry (ESI-MS) analysis is frequently associated with noncovalent adduct formation, both in positive and negative modes. Anion binding and sensing by mass spectrometry, notably more challenging compared to cation binding, will have major research potential with the development of appropriate sensors. Here, we demonstrated identification of stable bisquaternary dication adducts with trifluoroacetate (TFA), Cl and HSO in positive-mode ESI-MS analysis.
View Article and Find Full Text PDFThe design and synthesis of leu-enkephalin analogs by replacing the glycine residues with -(2-thioethyl)glycines and opening the cyclisation potential is presented. The cyclization (stapling) was achieved using bifunctional reagents (hexafluorobenzene and trithiocyanuric acid derivatives). The CD conformational studies of the stapled analogs suggest that the peptides adopt the type I β-turn conformation, which is in agreement with the theoretical analysis.
View Article and Find Full Text PDFThe fungal cell wall and cell membrane are an important target for antifungal therapies, and a needle-like cell wall or membrane disruption may be an entirely novel antifungal mode of action. In this work, we show how the coordination of Zn(II) triggers the antifungal properties of shepherin II, a glycine- and histidine-rich antimicrobial peptide from the root of Capsella bursa-pastoris. We analyze Cu(II) and Zn(II) complexes of this peptide using experimental and theoretical methods, such as: mass spectrometry, potentiometry, UV-Vis and CD spectroscopies, AFM imaging, biological activity tests and DFT calculations in order to understand the correlation between their metal binding mode, structure, morphology and biological activity.
View Article and Find Full Text PDFArgireline (Ac-EEMQRR-NH ), a well-known neurotransmitter peptide with a potency similar to botulinum neurotoxins, reveals a proven affinity toward Cu(II) ions. We report herein Cu(II) chelating properties of three new Argireline derivatives, namely, AN4 (Ac-EAHRR-NH ), AN5 (Ac-EEHQRR-NH ), and AN6 (Ac-EAHQRK-NH ). Two complementary experimental techniques, i.
View Article and Find Full Text PDFOuter membrane proteins of Fusobacterium nucleatum, a cancer‑leading bacteria, are considered as the factors responsible for its pathogenicity. Among them, homotrimeric autotransporter protein YadA (Yersinia adhesin A) is an important virulence factor also found in the outer membrane of pathogenic Yersinia species. In this paper, the structure and stability of certain Cu(II) complexes with YadA fragments were investigated using both, experimental and theoretical methods.
View Article and Find Full Text PDFPreeclampsia is a blood pressure disorder associated with significant proteinuria. Hypertensive women have increased levels of neurokinin B (NKB) and Cu(II) ions in blood plasma during pregnancy. NKB bears the ATCUN/NTS N-terminal motif empowering strong Cu(II) binding in a characteristic four-nitrogen (4N) square-planar motif, but an alternative Cu(II)NKB geometry was proposed earlier.
View Article and Find Full Text PDFIt is supposed that the presence of poly-His regions in close proximity to poly-Gly domains in snake venoms is related to their biological activity; poly-His/poly-Gly (pHpG) peptides inhibit the activity of metalloproteinases during venom storage via the chelation metal ions, necessary for their proper functioning. This work shows that only the histidyl residues from the N-terminal VDHDHDH motif (but not from the poly-His tag) were the primary Zn(II) binding sites and that the poly-Gly domain situated in the proximity of a central proline residue may play a regulatory role in venom gland protection. The proline induces a kink of the peptide, resulting in steric hindrance, which may modulate the accessibility of potential metal binding sites in the poly-His domain and may, in turn, be one of the regulators of Zn(II) accessibility in the venom gland and therefore a modulator of metalloproteinase activity during venom storage.
View Article and Find Full Text PDFArmodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due to its abuse by students and athletes, there is a need of its quantification. Quantitative analysis by liquid chromatography-mass spectrometry, however, though very common and sensitive, frequently cannot be performed without isotopically labeled standards which usually have to be specially synthesized.
View Article and Find Full Text PDFThe increasing number of antibiotic-resistant pathogens has become one of the foremost health problems of modern times. One of the most lethal and multidrug-resistant bacteria is (Mtb), which causes tuberculosis (TB). TB continues to engulf health systems due to the significant development of bacterial multidrug-resistant strains.
View Article and Find Full Text PDFHerein we present a synthesis and characterization of a new and unique low-weight heterocyclic compound 5-amino-2-(5-amino-3-methyl-1,2-oxazol-4-yl)-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-ylium bromide with the unusual electron charge delocalization owing the local positive charge at the carbon atom of oxadiazole moiety. X-ray single crystal of CHNO·Br showed the molecule crystalized in monoclinic, space group 2/. Both five membered rings are planar and twisted forming the ring motif with the counter ion where H⋯Br interactions are one of the dominant.
View Article and Find Full Text PDFIn many cases, human microbiota are associated with cancer progression. It was concluded that increases neoplastic changes. This bacterium is naturally present in human dental plaque.
View Article and Find Full Text PDFis one of the most notorious species involved in colorectal cancer. It was reported that numerous outer membrane proteins (OMP) are actively involved in carcinogenesis. In this paper, the structure and stability of certain complexes, as well as DNA cleavage and ROS generation by fragments of OMP, were investigated using experimental and theoretical methods.
View Article and Find Full Text PDFSpecific and nonspecific non-covalent molecular association of biomolecules is characteristic for electrospray-ionization mass spectrometry analysis of biomolecules. Understanding the interaction between two associated molecules is of significance not only from the biological point of view but also gas phase analysis by mass spectrometry. Here we reported a formation of non-covalent dimer of quaternary ammonium denatonium cation with +1 charge detected in the positive ion mode electrospray ionization mass spectrometry analysis of denatonium benzoate.
View Article and Find Full Text PDFThe increasing number of antibiotic-resistant pathogens has become one of the major health problems of modern times, including infections caused by . One of the possible mammalian immune system responses to mycobacterial infection is the increase of the zinc(II) concentration in phagosomes to a toxic level. The mycobacterial SmtB protein belongs to the family of ArsR/SmtB transcription regulators.
View Article and Find Full Text PDFCan a minor difference in the nonmetal binding sequence of antimicrobial clavanins explain the drastic change in the coordination environment and antimicrobial efficiency? This study answers the question with a definite "yes", showing the details of the bioinorganic chemistry of Zn(II) and Cu(II) complexes with clavanins, histidine-rich, antimicrobial peptides from hemocytes of the tunicate .
View Article and Find Full Text PDFThe aim of this study was to compare the antibacterial mode of action of silver ions (Ag) and selected silver nanoformulations against strains ( J53, BW25113 and its derivatives: Δ A, Δ C, Δ F, Δ R, ompRG596AcusSG1130A, cusSG1130A). In this research we used various experimental methods and techniques such as determination of the minimal inhibitory concentration, flow cytometry, scanning electron microscopy, circular dichroism as well as computational methods of theoretical chemistry. Thanks to the processing of bacteria and silver samples (ions and nanoformulations), we were able to determine the bacterial sensitivity to silver samples, detect reactive oxygen species (ROS) in the bacterial cells, visualize the interaction of silver samples with the bacterial cells, and identify their interactions with proteins.
View Article and Find Full Text PDFIt has been reported that numerous of Fusobacterium nucleatum outer membrane proteins take part in cancerogenesis. Therefore, it is very interesting to study their interactions with metal ions and the ability to produce reactive oxygen species, which may be involved in cancer progression. Since investigations of metal binding to proteins are often based on fragments that contain the metal-binding domains, designing model peptides should be very mindful.
View Article and Find Full Text PDFThe synthesis of new analogues of cyclolinopeptide A (CLA) and their linear precursors modified with (R)- and (S)-4-methylpseudoproline in the Pro-Pro fragment are presented. The peptides were tested in comparison with cyclosporine A (CsA) in concanavalin A (Con A) and pokeweed mitogen (PWM)-induced mouse splenocyte proliferation and in secondary humoral immune response in vitro to sheep erythrocytes (SRBC). Their effects on expression of selected signaling molecules in the Jurkat T cell line were also determined.
View Article and Find Full Text PDFReproduction of the dominant vector of Zika and dengue diseases, mosquito, is controlled by an active heterodimer complex composed of the 20-hydroxyecdysone receptor (EcR) and ultraspiracle protein. Although EcR shares the structural and functional organization with other nuclear receptors, its C-terminus has an additional long F domain (AaFEcR). Recently, we showed that the full length AaFEcR is intrinsically disordered with the ability to specifically bind divalent metal ions.
View Article and Find Full Text PDFPhleomycin is one of the anticancer glycopeptide antibiotics which cause DNA cleavage. It is commonly used as a copper(II) complex. Therefore, it is important to study the metal ion binding process and to define the coordination mode.
View Article and Find Full Text PDFGoserelin acetate (Gos) as a synthetic analog of the mammalian gonadotropin-releasing hormone (GnRH) is widely used in the treatment of sex hormone-related conditions. In this paper we present the chemical and biological aspects of its interaction with Cu(II) ions. The mode of Cu(II) binding and the thermodynamic stability of the obtained complexes were characterized by potentiometry, UV-Vis and CD spectroscopic methods.
View Article and Find Full Text PDFA number of fluorescent dyes based on BODIPY (4,4'-difluoro-4-bora-3a,4a-diaza-s-indacene) have been studied theoretically. This paper presents the results of calculations of these BODIPY dyes in their ground and excited states, performed using DFT and TD-DFT methods, respectively. The influences of N,N-dimethylaminobenzyl, ortho-fluorophenol, and methyl substituents as well as the solvent polarity on the positions of the absorption and emission bands of the dyes were analyzed.
View Article and Find Full Text PDFPolyhistidine-tags are often used for the affinity purification of polyhistidine-tagged recombinant proteins. These sequences are also found in nature and are often highly conserved across different species. However, their exact role in the biological systems is not clear.
View Article and Find Full Text PDFSnake venoms are complex mixtures of toxic and often spectacularly biologically active components. Some African vipers contain polyhistidine and polyglycine peptides, which play a crucial role in the interaction with metal ions during the inhibition of snake metalloproteases. Polyhistidine peptide fragments, known as poly-His tags, play many important functions, e.
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