M43 antibiotics: methylated vancomycins and unrearranged CDP-I analogs

Crystal Structures of the Complexes between Vancomycin and Cell-Wall Precursor Analogs

“…X-ray studies of vancomycin and related antibiotics have repeatedly confirmed "back-to-back" dimerization for vancomycin, [13][14][15][16][17] aglycovancomycin, 18 A-40926, 19 balhimycin, 20,21 deglucobalhimycin, 21 ureidobalhimycin, 22 and decaplanine, 23 except for monomeric degradation products such as the CDP-1 analog of vancomycin 24 and the CDP-1 analog of methylated vancomycin. 25 The formation of five hydrogen bonds between the antibiotic and the ligand has also been verified in the crystal structures of balhimycin or deglucobalhimycin complexes 21 with tripeptide or pentapeptide ligands with -D-Ala-DAla termini. These two complexes further revealed ligand-mediated "face-to-face" oligomerization.…”

Antibacterial activities and modes of action of vancomycin and related glycopeptides

“…Several close structural analogs of vancomycin have been reported recently, and these include A51568 factors A and B (14); the M43 group of antibiotics (25); A82846 factors A, B, and C (23); orienticins (35); chloroorienticins (34); eremomycin (6); and MM45289 (11).…”

“…In the vancomycin-type antibiotics, naturally occurring amino acid 1 is leucine or its methylated analogs (6,11,14,21,23,25,34,35). The state of methylation of the N-terminal leucine does not greatly affect the antibacterial activity of vancomycin.…”

“…M43F and M43B are the aspartic acid analogs of vancomycin and M43A, respectively (25). These two antibiotics are at least 10 times less active than vancomycin.…”

“…These two antibiotics are at least 10 times less active than vancomycin. CDP-1 (20), the rearranged isoaspartic acid analog of vancomycin, and the corresponding isoaspartic acid analog of M43A (25) are devoid of antibacterial activity.…”