1,276 research outputs found

    Investigation of the N-terminus amino functional of Arg10-Teixobactin

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    Teixobactin is a recently described antimicrobial peptide that shows high activity against gram-positive bacteria as well as mycobacterium tuberculosis. Due to both its structure as a head-to-side chain cyclodepsipeptide and its activity, it has attracted the attention of several research groups. In this regard, a large number of analogs with substitutions in both the cycle and the tail has been described. Here, we report the contribution of the N-terminus residue, N-Me-d-Phe, to the activity of Arg10-teixobactin. On the basis of our findings, we conclude that the N-terminus accepts minimum changes but not the presence of long alkyl chains. The presence of a positive charge is a requirement for the activity of the peptide. Furthermore, acylation of the N-terminus leads to total loss of activity

    Schistosoma mansoni cercarial elastase (SmCE): differences in immunogenic properties of native and recombinant forms

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    The Schistosoma mansoni cercarial elastase (SmCE) has previously been shown to be poorly immunogenic in mice. However, a minority of mice were able to produce antibodies against SmCE after multiple immunizations with crude pre- parations containing the enzyme. These mice were partially protected against challenge infections of S. mansoni. In the present study, we show that in contrast to the poor immunogenicity of the enzymatically active native form of SmCE derived from a crude preparation (cercarial transformation fluid), immunization of CBA/Ca mice with two enzymatically inactive forms, namely purified native SmCE or a recombinant SmCE fused to recombinant Schistosoma japonicum gluta- thione S-transferase (rSmCE-SjGST), after adsorption onto aluminum hydroxide adjuvant, induced specific anti-SmCE immunoglobulin G (IgG) in all mice within 2 weeks of the second immunization. The IgG antibody response to rSmCE- SjGST was mainly of the IgG1 subclass. These results suggest that inactive forms of the antigen could be used to obtain the optimum immunogenic effects as a vaccine candidate against schistosomiasis. Mice immunized with the rSmCE- SjGST on alum had smaller mean worm burdens and lower tissue egg counts when compared with adjuvant alone- and recombinant SjGST-injected controls. The native SmCE was antigenically cross-reactive with homologous enzymes of Schistosoma haematobium and Schistosoma margrebowiei

    Synthesis, X-ray structure, Hirshfeld surface analysis and antimicrobial assessment of tetranuclear s-triazine hydrazine Schiff base ligand

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    Funding: The Deputyship for Research and Innovation, “Ministry of Education”, King Saud University (IFKSUOR3-188-3), Saudi Arabia.The unexpected tetranuclear [Cu4(DPPT)2Cl6] complex was obtained by self-assembly of CuCl2.2H2O and (E)-2,4-di(piperidin-1-yl)-6-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1,3,5-triazine, ( HDPPT ) in ethanol. In this tetranuclear [Cu4(DPPT)2Cl6] complex, the organic ligand acts as mononegative chelate bridging two crystallographically independent Cu(II) sites. The DPPT− anion acts as a bidentate ligand with respect to Cu(1), while it is a tridentate for Cu(2). The Cu(1)N2Cl3 and Cu(2)N3Cl spheres have square pyramidal and square planar coordination geometries with some distortion, respectively. Two of the chloride ions coordinating the Cu(1) are bridging between two crystallographically related Cu(1) sites connecting two [Cu2(DPPT)Cl3] units together, leading to the tetranuclear formula [Cu4(DPPT)2Cl6]. The packing of the [Cu4(DPPT)2Cl6] complex is dominated by C-H
Cl contacts, leading to one-dimensional hydrogen-bond polymeric structure. According to Hirshfeld surface analysis of molecular packing, the non-covalent interactions H
H, Cl
H, Cl
C, C
H, and N
H are the most significant. Their percentages are 52.8, 19.0, 3.2, 7.7, and 9.7%, respectively. Antimicrobial assessment showed good antifungal activity of the Cu(II) complex against A. fumigatus and C. albicans compared to Ketoconazole as positive control. Moreover, the [Cu4(DPPT)2Cl6] complex has higher activity against Gram-positive bacteria than Gentamycin as positive control. The opposite was observed when testing the tetranuclear [Cu4(DPPT)2Cl6] complex against the Gram-negative bacteria.Publisher PDFPeer reviewe

    A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis

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    Programmed cell death or apoptosis is a central biological process that is dysregulated in many diseases, including inflammatory conditions and cancer. The detection and quantification of apoptotic cells in vivo is hampered by the need for fixatives or washing steps for non-fluorogenic reagents, and by the low levels of free calcium in diseased tissues that restrict the use of annexins. In this manuscript, we report the rational design of a highly stable fluorogenic peptide (termed Apo-15) that selectively stains apoptotic cells in vitro and in vivo in a calcium-independent manner and under wash-free conditions. Furthermore, using a combination of chemical and biophysical methods, we identify phosphatidylserine as a molecular target of Apo-15. We demonstrate that Apo-15 can be used for the quantification and imaging of drug-induced apoptosis in preclinical mouse models, thus creating opportunities for assessing the in vivo efficacy of anti-inflammatory and anti-cancer therapeutics

    Search for a vector-like quark Tâ€Č → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

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    A search for the electroweak production of a vector-like quark Tâ€Č, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first Tâ€Č search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet Tâ€Č states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a Tâ€Č quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength ÎșT = 0.25 and a relative decay width Γ/MTâ€Č < 5%

    Observation of the Rare Decay of the η Meson to Four Muons