Hydrophobic side-chain length determines activity and conformational heterogeneity of a vancomycin derivative bound to the cell wall of Staphylococcus aureus

Biochemistry
Sung Joon Kim, Jacob Schaefer

Abstract

Disaccharide-modified glycopeptides with hydrophobic side chains are active against vancomycin-resistant enterococci and vancomycin-resistant Staphylococcus aureus. The activity depends on the length of the side chain. The benzyl side chain of N-(4-fluorobenzyl)vancomycin (FBV) has the minimal length sufficient for enhancement in activity against vancomycin-resistant pathogens. The conformation of FBV bound to the peptidoglycan in whole cells of S. aureus has been determined using rotational-echo double resonance NMR by measuring internuclear distances from the (19)F of FBV to (13)C and (15)N labels incorporated into the cell-wall peptidoglycan. The hydrophobic side chain and aglycon of FBV form a cleft around the pentaglycyl bridge. FBV binds heterogeneously to the peptidoglycan as a monomer with the (19)F positioned near the middle of the pentaglycyl bridge, approximately 7 A from the bridge link. This differs from the situation for N-(4-(4-fluorophenyl)benzyl)vancomycin complexed to the peptidoglycan where the (19)F is located at the end of pentaglycyl bridge, 7 A from the cross-link.

References

Mar 1, 1995·Antimicrobial Agents and Chemotherapy·D A BeauregardD J Knowles
Feb 1, 2002·Journal of Magnetic Resonance·Robert D O'Connor, Jacob Schaefer
Feb 9, 2008·Journal of Molecular Biology·Sung Joon KimJacob Schaefer

Citations

May 8, 2009·Journal of the American Chemical Society·Shasad SharifJacob Schaefer
Jun 3, 2011·Journal of Medicinal Chemistry·Tucker C RobertsFloyd E Romesberg
Jun 5, 2014·Annual Review of Biophysics·Darón I Freedberg, Philipp Selenko
Jun 11, 2014·Biochimica Et Biophysica Acta·Sung Joon KimManmilan Singh
Jun 23, 2009·Journal of Molecular Biology·Sung Joon KimJacob Schaefer
Jul 7, 2009·Journal of Molecular Biology·Gary J PattiJacob Schaefer
Jul 22, 2009·Bioorganic & Medicinal Chemistry·Siegfried S F LeungWilliam L Jorgensen
Oct 14, 2010·Angewandte Chemie·Marie RenaultMarc Baldus
Sep 16, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Joseph A H Romaniuk, Lynette Cegelski
Feb 1, 2017·The Journal of Physical Chemistry. B·Robert D O'ConnorJacob Schaefer
Apr 4, 2017·The Journal of Physical Chemistry. B·Manmilan SinghSung Joon Kim
May 20, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Benjamin Valdez-SalasLidia Vargas-Osuna

Related Concepts

Carbon Radioisotopes
Cell Wall
Fluorine
Glycine, Sodium Hydrogen Carbonate
Pseudomurein
Protein Conformation
Staphylococcus aureus
AB-Vancomycin
Radiopharmaceuticals
Hydrophobicity

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