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The Chemistry of O-Polysaccharide Chains in Bacterial Lipopolysaccharides
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
The LPS of one of the common causes of vibriosis, V. anguillarum 02 (71), has been studied. It is one of 10 distinct serotypes of this species (Table 6). Its O-antigen polysaccharide has several unusual features, such as three different 2,3-diaminohexuronic acids (with d-gluco-, d-manno, and l-galacto configuration) and 2,4-diamino-2,4,6-trideoxy-d-glucose (bacillosamine). Vibrio cholerae is divided into Ol and non-Ol, where 01 is the major causative agent for cholera. Unusual structures were found for the V. cholerae 076 (72) and 0144 (73) antigens. Thus, they are homopolymers built up of 4-amino-4,6-dideoxy-l-mannose l-perosamine residues, in contrast to 01 which is a homopolymer of d-perosamine. The acid forming the amide in 01 is 3-deoxy-l-glycero-tetronic acid (or (S)-2,4-dihydroxybutanoic acid), but for 076 it was (S)-2-hydroxypropionic acid, and in 0144 (R)-(2-hydroxyl)-propionic acid. As expected, no serological cross-reaction was observed between 01 and the two other species.
Mass Spectrometric Analysis
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Kijanimicin has been shown to have a novel tetronic acid structure [183]. The californium-252 PD mass spectrum established the molecular weight to be 1316.6 after attempts with EI, CI, and FD failed. Plasma desorption mass spectrometry was also used to determine the molecular weight of the macrolide after the tetrasaccharide group was removed by mild hydrolysis.
Discovery of natural products with metal-binding properties as promising antibacterial agents
Published in Expert Opinion on Drug Discovery, 2019
Prasad Dandawate, Subhash Padhye, Rainer Schobert, Bernhard Biersack
Tetronic acids which are O-analogs of tetramic acids were isolated from bacteria, moulds, algae, fungi, lichens and sponges [64,96,97]. Ascorbic acid (48a, vitamin C) is probably the most prominent tetronic acid. Though not carrying a 3-acyl residue it is a strong metal chelator due to its endiol moiety. While 48a is only a weak inhibitor (IC50 = 6100 µM) of SagHyal4755 which is a bacterial surface protein and hyaluronidase of Streptococcus agalactiae associated with the rupture of host extracellular matrix, its hexadecanoyl derivative 48b (IC50 = 4.2 µM) and octadecanoyl derivative 48c (IC50 = 0.9 µM) showed much higher inhibitory activity (Figure 5) [98]. The fatty acyl side chains of 48b and 48c fit snugly into a hydrophobic channel of the enzyme leading to the improved affinity when compared with 48a. Synthetic 3-acyltetronic acids 49a and 49b showed stronger agr-inhibiting properties (IC50 = 3–6 µM) than the closely related 3-acyltetramic acids 40b-d (Figure 5) [76]. Agglomerin A (50), isolated from Enterobacter agglomerans PB-6042, displayed antibacterial activity against gram-positive and gram-negative bacteria including C. difficile, B. fragilis, B. vulgatus, Streptococcus constellatus (MIC = 3.13 µg/mL) and Eubacterium limosum, B. longum, B. melaninogenicus, F. nucleatum, F. necrophorum (MIC = 6.25 µg/mL) (Figure 5) [64]. The ionophoric tetronomycin (51) isolated from Streptomyces in 1982 features a more complex 3-acyl side chain and is strongly antibiotic against gram-positive bacteria (MIC < 0.3 µg/mL) [96,97]. Tetrocarcin spirotetronates such as tetrocarcin A (52) were selectively active against gram-positive bacteria (MIC = 0.1 µg/mL from B. subtilis, MIC = 20 µg/mL from S. aureus) while they proved inactive against gram-negative strains (MIC > 100 µg/mL). The aglycone, i.e., (+)-tetronolide, was synthesized by Boeckman Jr. and coworkers using a ketene-trapping/intramolecular [4 + 2] cycloaddition strategy (Figure 5) [64,99]. Structurally related natural spirotetronates with high antibacterial activity are kijanimicin (MIC = 0.86 µg/mL in Propionibacterium acne, MIC < 0.13 µg/mL in B. subtilis) and maklamicin (MIC = 0.2–13 µg/mL in gram-positive bacteria) [97]. Abyssomycin C (53) was isolated from Verrucosispora, an actinomycete dwelling in sediment of the Japanese sea abyss, and exhibited activity against gram-positive bacteria (MIC = 4 µg/mL in MRSA, MIC = 13 µg/mL in VRSA) and M. tuberculosis (MIC = 3.6 µM) [97,100]. It is assumed that the Michael enone system of abyssomycin C is decisive for its antibacterial activity since close analogs such as abyssomycin B and D, which lack this enone system, were inactive. Metal chelation is unlikely to play a role in its bioactivity due to the non-planarity of the β-dicarbonyl system.