Structures of the Muraymycins, Novel Peptidoglycan Biosynthesis Inhibitors

Abstract

The muraymycins, a family of nucleoside-lipopeptide antibiotics, were purified from the extract of Streptomyces sp. LL-AA896. The antibiotics were purified by chromatographic methods and characterized by NMR spectroscopy, degradation studies, and mass spectrometry. The structures of 19 compounds were established. The muraymycins constitute a new antibiotic family whose core structure contains a glycosylated uronic acid derivative joined by an aminopropane group to a hexahydro-2-imino-4-pyrimidylglycyl residue (epicapreomycidine) containing dipeptide that is further extended by a urea-valine moiety. Members of this family show broad-spectrum in vitro antimicrobial activity against a variety of clinical isolates (MIC 2 to >64 mug/mL). The muraymycins inhibited peptidoglycan biosynthesis. The fatty acid substituent and the presence or absence of the amino sugar play important roles in biological activity. One of the most active compounds, muraymycin A1, demonstrated protection in vivo against Staphylococcus aureus infection in mice (ED50 1.1 mg/kg).

Caprazamycins, Novel Lipo-nucleoside Antibiotics, from Streptomyces sp.

“…The CPZs are structurally related to lipo-uridyl antibiotics such as liposidomycins, muraymycins [12] and capuramycins [13ϳ15], which have been shown to be specific inhibitors of a bacterial translocase. Liposidomycins are especially, close analogs of CPZs, differing in the absence of the tri-O-methyl-L-rhamnose moiety and the dissimilarity for configuration of the acylated side chain at the C-3a position [5].…”

“…TLC (2 : 1 : 1 EtOAc -1-PrOH -20% aq AcOH) of the solution showed two spots at Rf 0.95 (12) and 0.05 (11) (cf. 8: Rf 0.35).…”

Synthesis and properties of DNA oligonucleotides with a zwitterionic backbone structure

“…Muraymycins represent a promising class of natural products with antimicrobial activity. 24 In the course of our synthetic investigations on muraymycins, [25][26][27] we have previously reported on the efficient stereoselective preparation of protected forms of 4 and have coined the term nucleosyl amino acids (NAAs) for these types of compounds. 28,29 However, if one merges the structural principles of 4 with an amide internucleotide bridge of type 1, an oligonucleotide modification of type 5 ('NAA-modification') is obtained.…”

A novel assay of bacterial peptidoglycan synthesis for natural product screening

“…Then, phospho-N-acetylmuramyl-pentapeptide translocase (translocase I, MraY) catalyzes the transfer of the MurNAcpentapeptide moiety to the lipid carrier undecaprenyl phosphate to form lipid I. To date, a variety of nucleoside antibiotics have been reported as translocase I inhibitors, 5 such as mureidomycins, 6 pacidamycins, 7 napsamycins, 8 liposidomycins, 9 tunicamycin, 10 capuramycins, 11-17 muraymycins 18 and caprazamycins. 19,20 In contrast, only a few inhibitors have been reported for the steps of UDP-MurNAc-pentapeptide formation.…”