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Direct determination of solution binding constants for noncovalent complexes between bacterial cell wall peptide analogues and vancomycin group antibiotics by electrospray ionization mass spectrometry

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UNSPECIFIED (1998) Direct determination of solution binding constants for noncovalent complexes between bacterial cell wall peptide analogues and vancomycin group antibiotics by electrospray ionization mass spectrometry. ANALYTICAL CHEMISTRY, 70 (20). pp. 4427-4432. ISSN 0003-2700

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Abstract

We report a method based on electrospray ionization (ESI) mass spectrometry to determine solution association constants (KA) for complexes between glycopeptide antibiotics (vancomycin and ristocetin) and several peptide ligands. The measured KA values are in good agreement with previously reported values obtained by standard spectroscopic titration techniques. The pH stability of the ristocetin-diacetyl-L-lysyl-D-alanyl-D-alanine complex was investigated by ESI mass spectrometry and circular dichroism (CD) spectroscopy. The two methods produce very similar results, demonstrating that the ESI mass spectra reflect the pH stability of the complex. In solution, the antibiotics bind stereospecifically to peptides containing a C-terminal D-Ala-D-Ala sequence, whereas no complex formation is observed with peptides containing the L-Ala-L-Ala stereoisomer. To investigate whether electrospray ionization is able to reflect the structurally specific interaction between antibiotics and D-Ala-D-Ala peptide ligands, an equimolar mixture of vancomycin, diacetyl-L-lysl-D-alanyl-D-alanine, and the deuterium-labeled stereoisomer diacetyl-L-lysyl-L-alanyl-L-alanine-d(6) was analyzed by ESI mass spectrometry. In agreement with solution-phase behavior, only ions corresponding to a complex between diacetyl-L-lysyl-D-alanyl-D-alanine and vancomycin are observed.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
Journal or Publication Title: ANALYTICAL CHEMISTRY
Publisher: AMER CHEMICAL SOC
ISSN: 0003-2700
Date: 15 October 1998
Volume: 70
Number: 20
Number of Pages: 6
Page Range: pp. 4427-4432
Publication Status: Published
URI: http://wrap.warwick.ac.uk/id/eprint/15287

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