This change in hydrogen bonding pattern is all the bacteria needs to survive. Interestingly changing an oxygen in vancomycin aglycone (compound 5 below) to an NH (compound 6 below) restores activity against VRE, strains with D-Ala-D-Lac, and compound 6 is still active against strains with (D-Ala-D-Ala). Why? OH MIC compd (ug/mL) HO OH 5 N NHMe 640 0.31 31 O 6 7 " NH HM 8 >640 HO,C9 - OH 5 Y = 0 6. Y = NH 7. Y = H2 8. Y=S a VanA VRE HO From JACS 2011, 133, 13946 by Boger et al. This change in hydrogen bonding pattern is all the bacteria needs to survive. Interestingly changing an oxygen in vancomycin aglycone (compound 5 below) to an NH (compound 6 below) restores activity against VRE, strains with D-Ala-D-Lac, and compound 6 is still active against strains with (D-Ala-D-Ala). Why? OH MIC compd (ug/mL) HO OH 5 N NHMe 640 0.31 31 O 6 7 " NH HM 8 >640 HO,C9 - OH 5 Y = 0 6. Y = NH 7. Y = H2 8. Y=S a VanA VRE HO From JACS 2011, 133, 13946 by Boger et al