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finished adding references to the mech of action and structure
Vancomycin kills and prevents the growth of gram-positive bacteria by inhibiting the cell-wall synthesis of these bacteria <ref name="Reynolds" />. The cell walls of gram-positive bacteria are comprised of several layers of peptidoglycan, a mesh-like polymer made up of sugars and amino acids. It is this layer that provides the necessary mechanical support for bacteria to be able to withstand fluctuations in osmotic pressures in excess of 5-15 atm without lysing (rupturing)<ref name="Kahne"> Kahne, D., Leimkuhler, C., Lu, W. & Walsh, C. (2005). Glycopeptide and Lipoglycopeptide Antibiotics. Chemical Reviews, 105, 425-448. </ref> .
A single peptidoglycan layer consists of many crosslinked glycan chains. A glycan chain is made up of repeating units of covalently bonded N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) monomers joined together through transglycosylation. The newly elongated chains are mechanically weak till the pentapeptide chains found on every NAM molecule are crosslinked. This is done by a family of transpeptidases, which use the amide group of the Lys3 on one strand to attack the D-Ala4 on the other strand, liberating a D-Ala5 residue, and forming a Lys3-D-Ala4 interstrand isopeptide bond which acts as a strengthening covalent cross-link between the two strands. [4] <ref name="Kahne" />
Vancomycin belongs to a class of antibiotics which interferes in both the polymerization and the cross linking of glycan strands. It does this by binding firmly to the substrate of the transpeptidation enzymes, the D-Ala4-D-Ala5 dipeptide, by means of five hydrogen bonds with its peptide backbone <ref name="Reynolds" /> <ref name="Bam"> Bambeke, F. van, Laethem, Y. van, Courvalin, P. & Tulkens, P.M. (2004) Glycopeptide Antibiotics from Conventional Molecules to New Derivatives. Drugs, 64(9), 913-936. </ref>. The formation of this complex prevents both transglycosylation and transpeptidation via steric hindrance [5]<ref name="Bam" />.
The final two steps of bacterial peptidoglycan biosynthesis constitute a good target for any antimicrobial agent, as both processes are extracellular and thus accessible to compounds that are unable to penetrate the cell membrane. Furthermore, the peptidoglycan layer is vital 2ugh to survival that it is highly conserved across organisms, meaning that compounds such as vancomycin are effective against a variety of gram-positive bacteria. Lastly, targeting a process that involves multiple, related enzymes is advantageous as a single, spontaneous mutation in one enzyme will not lead to resistance. [4]<ref name="Kahne" />
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