5'-DMT-T(C6 Amino)-Suc-CPG; 500 Å

Proteins with a Zn(II)₂Cys₆ domain, Cys-X₂-Cys-X₆-Cys-X₅₋₁₂-Cys-X₂-Cys-X₆₋₉-Cys (hereafter, referred to as the C6 domain), form a subclass of zinc finger proteins found exclusively in fungi and yeast. Genome sequence databases of Saccharomyces cerevisiae and Candida albicans have provided an overview of this family of genes. Annotation of this gene family in most fungal genomes is still far from perfect and refined bioinformatic algorithms are urgently needed. Aspergillus flavus is a saprophytic soil fungus that can produce the carcinogenic aflatoxin. It is the second leading causative agent of invasive aspergillosis. The 37-Mb genome of A. flavus is predicted to encode 12,000 proteins. Two and a half percent of the total proteins are estimated to contain the C6 domain, more than twofold greater than those estimated for yeast, which is about 1 %. The variability in the spacing between cysteines, C₃-C₄ and C₅-C₆, in the zinc cluster enables classification of the domains into distinct subgroups, which are also well conserved in Aspergillus nidulans. Sixty-six percent (202/306) of the A. flavus C6 proteins contain a specific transcription factor domain, and 7 % contain a domain of unknown function, DUF3468. Two A. nidulans C6 proteins containing the DUF3468 are involved in asexual conidiation and another two in sexual differentiation. In the anamorphic A. flavus, a homolog of the latter lacks the C6 domain. A. flavus being heterothallic and reproducing mainly through conidiation appears to have lost some components involved in homothallic sexual development. Of the 55 predicted gene clusters thought to be involved in production of secondary metabolites, only about half have a C6-encoding gene in or near the gene clusters. The features revealed by the A. flavus C6 proteins likely are common for other ascomycete fungi.

High-throughput metabolite profiling provides the opportunity to reveal metabolic mechanisms and identify biomarkers. Psoriasis is an immune-mediated chronic inflammatory disease. However, the role of metabolism in psoriasis pathogenesis remains unclear. Methods: Plasma samples of individuals (45 psoriasis and 45 sex-, age-, and BMI-matched healthy controls) were collected. Non-targeted metabolomics and amino acid- or carnitine-targeted metabolomics were conducted, then, plasma samples of mice induced by imiquimod (IMQ) were subjected to the amino acid- and carnitine-targeted metabolomic profiling. Flow cytometry was used to study the effect of L-carnitine (LC(C0)) on IMQ-induced psoriatic inflammation. Results: Through the non-targeted metabolomics approach, we detected significantly altered amino acids and carnitines in psoriasis patients. Amino acid-targeted metabolomic profiling identified 37 amino acids altered in psoriasis, of these 23 were markedly upregulated, including essential amino acids (EAAs), and branched-chain amino acids (BCAAs), whereas glutamine, cysteine, and asparagine were significantly down-regulated. Carnitine-targeted metabolomic profiling identified 40 significantly altered carnitines, 14 of which included palmitoylcarnitine (C16) and were markedly downregulated in psoriasis, whereas hexanoylcarnitine (C6) and 3-OH-octadecenoylcarnitine (C18: 1-OH) were significantly upregulated. Interestingly, glutamine, asparagine, and C16 levels were negatively correlated with the PASI score. Moreover, a higher abundance of LC(C0) was associated with markedly reduced IMQ-induced epidermal thickening and infiltration of Th17 cells in skin lesions, indicating LC(C0) supplementation as a potential therapy for psoriasis treatment. Conclusion: Our results suggested the metabolism of amino acids and carnitines are significantly altered in psoriasis, especially the metabolism of EAAs, BCAAs, and LC(C0), which may play key roles in the pathogenesis of psoriasis.

In this paper, the biologically inert agarose was selectively modified at C6 of β-d-Galp units to produce an amino derivative with antibacterial property. The synthetic route involved the preparation of tosyl and azido agarose intermediates. All the polysaccharide derivatives were characterized by mono- and bidimensional 1H and 13C NMR and FT-IR analysis. A water-soluble amino polymer (Mw = 39,000 g mol-1, DSamino = 0.50) was produced by partial acid hydrolysis showing bactericidal and bacteriostatic activity against P. aeruginosa (ATCC 9027), S. aureus (ATCC 6538), and E. coli (ATCC 25922), with MIC values lower than 2.5 mg mL-1 and MBC values ranging from 2.5 to 5.0 mg mL-1.