Disease relevance of Polyoxins

• This aminoaldonic acid is the N terminus of the nucleoside peptide antibiotics, the polyoxins, produced by Streptomyces cacaoi var. asoensis [1].

High impact information on Polyoxins

• Chitin synthase inhibitors have been studied through chemical modification of the polyoxins and nikkomycins but are limited because of unfavorable pharmacokinetics [2].
• The activity also had a pH optimum of 7.5, was most stimulated by Mg(2+), and was more inhibited by polyoxin D than by nikkomycin Z [3].
• The synthesis and biological properties of seven polyoxins (4-10) designed to avoid peptidase hydrolysis in Candida albicans are presented [4].
• At concentrations up to 2 mM these two new polyoxins were ineffective in the inhibition of cell growth or reduction of cell viability, but they induced aberrant morphologies in C. albicans at a concentration of 0.25 mM [5].
• Five dipeptidyl and two tripeptidyl polyoxin analogues were synthesized by coupling an amino acid active ester or azlactone to uracil polyoxin C (2) or polyoxin D (1), subsequent removal of the protecting group, and purification by preparative HPLC [4].

Chemical compound and disease context of Polyoxins

• The addition of these substrates to Streptomyces cacaoi led to the isolation of polyoxins from which 3-ethylidene-L-azetidine-2-carboxylic acid was isolated by hydrolysis [6].

Biological context of Polyoxins

• These data suggest that polyoxins containing hydrophobic amino acids retain strong chitin synthetase inhibitory activity and are resistant to cellular hydrolysis [5].
• Chitin synthetase was competitively inhibited by polyoxin D (Ki 6.5 muM) and (Ki 1.35 mM), the latter giving complex kinetics [7].
• These results demonstrated that the morphological alterations caused by polyoxin D were due to the absence of chitin, a wall component important for formation of primary septa and for maintenance of structural integrity during morphogenesis [8].
• The most widely studied chitin synthase inhibitors are polyoxins and nikkomycins that probably bind to the catalytic site of chitin synthases [9].

Anatomical context of Polyoxins

• Inhibition of chitin synthesis in the cell wall of Coccidioides immitis by polyoxin D [10].
• Polyoxin D also prevents the appearance of enhanced fluorescence at the junction between mother cell and bud, as observed in the presence of a brightener [11].
• Rgenerating protoplasts are less affected by polyoxin D [12].
• Adhesion of Candida albicans to epithelial cells effect of polyoxin D [13].

Associations of Polyoxins with other chemical compounds

• Chs2 also shows less sensitivity than Chs1 to inhibition by polyoxin D or sodium chloride, a property that was used to demonstrate the presence of Chs2 in wild-type extracts [14].
• 1. Diflubenzuron and polyoxin D clearly inhibited the incorporation of [3H]-N-acetylglucosamine ([3H]NAGA) into chitin in the isolated integument from newly molted American cockroaches under the experimental condition [15].

Gene context of Polyoxins

• Larvae fed on the potent chitin synthase inhibitor polyoxin D or the chitin-binding agent Calcofluor White, showed strong concentration-dependent inhibition of larval weight and survival but no discernible effects on the matrix structure [16].
• The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase [17].

Analytical, diagnostic and therapeutic context of Polyoxins

• Flow cytometry analyses of yeasts revealed 2 peaks of fluorescence intensity, and pointed to differences between polyoxin D treated and non-treated microorganisms [13].

References