Antibiotic resistance is a growing problem. The antibiotic Vancomycin binds via hydrogen bonding to D-ala-D-ala which is part of an intermediate in Bacterial Cell wall Biosynthesis. Please indicate all possible hydrogen bond acceptor and donor sites on D-Ala-D-Ala below (Note that D-Ala is just the enantiomer of the naturally occurring amino acid L-Ala.) . N HEN CH Bacteria have gain resistance to vancomycin, e.g. vancomycin resistant enteroccoci (VRE), by changing D-Ala-D-Ala to D-Ala-D-Lac where D-lac is D-lactate. Please indicate all possible hydrogen bond acceptor and donor sites on D-Ala-D-Lac below CHS HN OH CH Please indicate how water might hydrogen bond with D-Ala-D-Ala CHE H N IN OH CH Please indicate how water might hydrogen bond with D-Ala-D-Lac . HAN OH CH, 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. Antibiotic resistance is a growing problem. The antibiotic Vancomycin binds via hydrogen bonding to D-ala-D-ala which is part of an intermediate in Bacterial Cell wall Biosynthesis. Please indicate all possible hydrogen bond acceptor and donor sites on D-Ala-D-Ala below (Note that D-Ala is just the enantiomer of the naturally occurring amino acid L-Ala.) . N HEN CH Bacteria have gain resistance to vancomycin, e.g. vancomycin resistant enteroccoci (VRE), by changing D-Ala-D-Ala to D-Ala-D-Lac where D-lac is D-lactate. Please indicate all possible hydrogen bond acceptor and donor sites on D-Ala-D-Lac below CHS HN OH CH Please indicate how water might hydrogen bond with D-Ala-D-Ala CHE H N IN OH CH Please indicate how water might hydrogen bond with D-Ala-D-Lac . HAN OH CH, 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