Althusser and the Critique of Political Economy

Two disulfide-containing peptides, barrettides A (<b>1</b>) and B (<b>2</b>), from the cold-water marine sponge <i>Geodia barretti</i> are described. Those 31 amino acid residue long peptides were sequenced using mass spectrometry methods and structurally characterized using NMR spectroscopy. The structure of <b>1</b> was confirmed by total synthesis using the solid-phase peptide synthesis approach that was developed. The two peptides were found to differ only at a single position in their sequence. The three-dimensional structure of <b>1</b> revealed that these peptides possess a unique fold consisting of a long β-hairpin structure that is cross-braced by two disulfide bonds in a ladder-like arrangement. The peptides are amphipathic in nature with the hydrophobic and charged residues clustered on separate faces of the molecule. The barrettides were found not to inhibit the growth of either <i>Escherichia coli</i> or <i>Staphylococcus aureus</i> but displayed antifouling activity against barnacle larvae (<i>Balanus improvisus</i>) without lethal effects in the concentrations tested

Stabilized Cyclic Peptides as Scavengers of Autoantibodies: Neutralization of Anticitrullinated Protein/Peptide Antibodies in Rheumatoid Arthritis

The occurrence of autoantibodies is a hallmark of rheumatoid arthritis, specifically those autoantibodies targeting proteins containing the arginine-derived amino acid citrulline. There is strong evidence showing that the occurrence of anticitrullinated protein/peptide antibodies (ACPA) are involved in disease progression, and ACPA was recently shown to induce pain in animals. Here, we explore a novel concept useful for research, diagnostics, and possibly therapy of autoimmune diseases, namely, to directly target and neutralize autoantibodies using peptide binders. A high-affinity peptide-based scavenger of ACPA was developed by grafting a citrullinated epitope derived from human fibrinogen into a naturally occurring stable peptide scaffold. The best scavenger comprises the truncated epitope α-fibrinogen, [Cit573]­fib(566–580), grafted into the scaffold sunflower trypsin inhibitor-1, SFTI-1. The final peptide demonstrates low nanomolar apparent affinity and superior stability

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Sri Lanka is a biodiversity hotspot and one of the richest geographical locations of marine sponges in the Indian ocean. However, the most extensive taxonomical study on Sri Lankan sponge biodiversity dates back ~100 years and only a limited number of studies have been conducted on sponge natural products. In the current study, 35 marine sponge specimens (collected from 16 sponge habitats around Sri Lanka) were identified, microfractionated and evaluated for antibacterial and anticancer assays. In total, 30 species were characterized, of which 19 species gave extracts with antibacterial and/or cytotoxic activities. Microfractionated organic extract of Aciculites orientalis gave the most potent antibacterial activity against Staphylococcus aureus and strongest lymphoma cell toxicity was exhibited by the organic extract of Acanthella sp. Guided by the molecular ion peaks in the bioactive fractions, large-scale extraction of Stylissa massa led to the isolation of three bromopyrrole alkaloids, sceptrin, hymenin and manzacidin A/C. Of these, sceptrin exhibited broad spectrum antibacterial activity against both Escherichia coli and S. aureus (MIC of 62.5 μM against both species). Based on natural product literature, seven promising species were identified as understudied. Their further exploration may lead to the discovery of structurally novel compounds.</div

Results of FMCA against the histiocytic human lymphoma cell line U-937.

Results of FMCA against the histiocytic human lymphoma cell line U-937.</p

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Includes images of the sponge species investigated in the current study, map of sponge sample collection sites in Sri Lanka, results of the agar disc diffusion assay, microfractionation exemplified by the isolation and identification of bromopyrrole alkaloids from Stylissa massa, a summary of sponge extracts that gave no antibacterial activity in the disc diffusion and microdilution assays and a literature review of antibacterial and cytotoxic compounds identified in previous reports for the same sponge species as in the current study. (DOCX)</p

Structures of bromopyrrole alkaloids isolated from <i>Stylissa massa</i>.

(1) Sceptrin; (2) Hymenin; (3) Manzacidin A/C. All structures were confirmed by comparison of spectral data to previously published values [24–29].</p

The bioassay guided microfractionation protocol followed for the identification of molecular ions in sponge extracts, exemplified by <i>Erylus</i> sp.

A: The RP-HPLC chromatogram of microfractionated aqueous extract of Erylus sp. (254 nm) with the antibacterial region highlighted in a red square. B: The RP-HPLC chromatogram of the microfractionated organic extract of Erylus sp. (254 nm). C: The dominant molecular ions in bioactive fraction 37 of Erylus sp. D: The microdilution assay against S. aureus for Erylus sp. showing bacterial inhibition down to a two-fold dilution for the fractions 34 and 38 (inhibition in the first two wells from left), down to a four-fold dilution for the fractions 35 and 36 (inhibition in the first three wells from left), down to a sixteen-fold dilution for the fraction 37 (inhibition down to five wells from left) and fraction 39 with no dilution (inhibition only in the first well from the left).</p

Schematic diagram of the strategy used in marine sponge specimen identification and compound isolation from <i>Stylissa massa</i>.

Once the molecular ions associated with the antibacterial fractions were identified through the bioassay-guided microfractionation protocol, Stylissa massa was extracted in large scale, resulting in the isolation and structural characterization of bromopyrrole alkaloids. The underwater picture of Stylissa massa represents specimen 200220-01-11 which was used for large-scale extraction.</p

Summary of the antibacterial activity of sponge specimens subjected to disc diffusion and micro dilution assays.

Summary of the antibacterial activity of sponge specimens subjected to disc diffusion and micro dilution assays.</p

Details of the specimens investigated: Species identification, location (locality name and coordinates), depth of collection (in meters), voucher museum numbers and GenBank accession numbers.

Details of the specimens investigated: Species identification, location (locality name and coordinates), depth of collection (in meters), voucher museum numbers and GenBank accession numbers.</p