Structures of neopolyoxins A, B, and C

Uramoto, Masakazu; Kobinata, Kimie; Isono, Kiyoshi; Higashijima, Tsutomu; Miyazawa, Tatsuo; Jenkins, E.E.; McCloskey, James A.

doi:10.1016/s0040-4039(00)78698-9

Cited by 53 publications

(26 citation statements)

References 9 publications

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“…While the native nikkomycin Z, with its methyl group at the beta position of the amino acid, was able to resist degradation over the 6-h assay period, derivatives with a hydroxy group were largely degraded. Independent of enzymatic degradation, it was discovered that the peptide bonds of nikkomycins Z, X, and J were unstable at neutral and alkaline pHs, similar to what had been described for neopolyoxins (252).…”

Section: Compounds Active Against Fungal Cell Walls Inhibitors Of Chimentioning

confidence: 59%

“…Although the nikkomycins have been extensively evaluated for commercial development, no product has reached the marketplace. Subsequent to the discovery of the nikkomycins, a subspecies of S. cacaoi was discovered to produce a number of secondary metabolites termed neopolyoxins that were essentially identical in structure to the nikkomycins (252,253).…”

Section: Compounds Active Against Fungal Cell Walls Inhibitors Of Chimentioning

confidence: 99%

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Compounds active against cell walls of medically important fungi

Hector

1993

Clin Microbiol Rev

215

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A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development.

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Section: Compounds Active Against Fungal Cell Walls Inhibitors Of Chimentioning

confidence: 59%

Section: Compounds Active Against Fungal Cell Walls Inhibitors Of Chimentioning

confidence: 99%

Compounds active against cell walls of medically important fungi

Hector

1993

Clin Microbiol Rev

215

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“…This effect has already been observed in previous studies on the structure of the neopolyoxins, which exhibit the same N-terminal amino acid as nikkomycins Z and X (Uramato et al, 1980). It was suggested that the instability of the peptide bond of the neopolyoxins is caused by the position of the adjacent yhydroxyl group and nitrogen of the hydroxypyridine ring (Uramoto et al, 1980). Nikkomycins W,, Wz, Bx and BZ, which contain a hydroxyphenyl ring instead of a hydroxypyridyl residue, are stable at neutral and alkaline PH.…”

Section: Inhibition Of Chitin Synthase Of Coprinus Cinereusmentioning

confidence: 99%

Structure-activity relationships of the nikkomycins

Decker

Zähner

Heitsch

et al. 1991

Journal of General Microbiology

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The structure-activity relationships of different nikkomycins were studied to evaluate the structural requirements for a potent chitin synthase inhibitor. We investigated the transport of the nikkomycins via the peptide transport system of the yeast Yarrowia fipoiytica and determined the kinetic parameters for nikkomycin Z uptake [Km = 24 PM, Vmax = 2.2 nmol min-l (mg dry wt)-l]. We demonstrated that the @-methyl group of the N-terminal amino acid of dipeptide nikkomycins protects the molecule against peptidase activity in crude cell-extracts of different fungi. Furthermore, the relationship between inhibition constants for chitin synthase, transport of the nikkomycins via the peptide transport system, susceptibility to degradation by cellular proteases and whole-cell activity of the nikkomycins are discussed.

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“…ȕ-Acetamido ketones are valuable building blocks for the preparation of ȕ-amino ketones or ȕ-amino alcohols such as antibiotic nikkomycins [1,2] and neopolyoxines [3]. Į-acetamido ketones in Dakin-West reaction [4] and ȕ-acetamido ketones in Iqbal route are obtained [5,6].…”

Section: Introductionmentioning

confidence: 99%