Pradimicin Resistance of Yeast Is Caused by a Mutation of the PutativeN-Glycosylation Sites of Osmosensor Protein Sln1

Antiviral Activity of Synthetic Aminopyrrolic Carbohydrate Binding Agents: Targeting the Glycans of Viral gp120 to Inhibit HIV Entry

“…[4c,d] Therefore, the development of small-size nonpeptidic molecules as CBAs is emerging as ap romising strategy for antiviral therapies and vaccines. For example, the nonpeptidic antibiotic pradimicin A( PRM-A) and its more soluble analogue pradimicin S( PRM-S), which have been found to bind to the terminal mannosides exposed on fungal membranes, [7,8] show antiviral activity against HIV-1, with 50 %e ffective concentrations (EC 50 ) in the low micromolar range (PRM-A EC 50 = 3.33 mm). [9a-c] Nonpeptidic 1,3,5-triazines, shown to bind to gp120a nd to inhibit HIV-1 in cell culture, have also been reported, [9d] as well as glycan-binding benzoboroxole-functionalized polymers.…”

Problems and hopes in the development of drugs targeting the fungal cell wall

“…The only inhibitors reported to date in the literature are substrate analogs that are active in vitro in membrane preparations but poorly active in vivo in the fungus. Other inhibitors target only one class of CHS [4,5]. Glycosylhydrolase and transglycosidase families often contain many genes, which are able to remodel the linear polysaccharides synthesized by the respective synthases (Figure 3) protein/glycosylphospholipid-anchored surface protein family that display the same b-(1,3)-glucanosyltransferase activity but can be either dispensable or essential for the fungus [8][9][10].…”

“…However, in contrast to bacteria, where the peptidoglycan, an equivalent of the fungal cell wall, is the target of many classes of antibacterial agents [2], only a single class of drugs has been developed that targets the fungal cell wall [3]; these are the echinocandins that block b-(1,3)-glucan synthesis in a non competitive manner. Other inhibitors of chitin and mannan synthesis have been identified but none of these have yet reached the clinic [4][5][6]. Even for the echinocandins that have demonstrated their activity against fungi, the precise mode of action of these compounds has not been elucidated [7].…”

Premithramycinone G, an Early Shunt Product of the Mithramycin Biosynthetic Pathway Accumulated upon Inactivation of Oxygenase MtmOII

“…Thus, 4 must be viewed as a dodecaketide-derived compound, which relates it to the group of benanomicin/pradimicin-type antifungal antibiotics. [28][29][30][31][32][33][34] However, an incorporation experiment with [1,2-13 C]acetate showed that only the first 10 acetate units of 4 were 13 C-enriched, while 3 carbon atoms of the oxobutyryl side chain did not appear to be labeled (Scheme 3). These results may indicate that the three unlabeled carbon atoms derive either from another biosynthetic pool (for example, acetoacetate from incompletely degraded fatty acids) or are acetate-derived, but come in at a much later stage of the biosynthesis pathway, which was not (or no longer) affected by the exogenously fed 13 C-labeled acetate-possibly after the closure of the first three rings of the molecule.…”