ISSN:
1076-5174
Keywords:
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
,
Physics
Notes:
Non-covalent binding of antibiotics to their target ligands represents a form of molecular recognition which is of considerable contemporary interest in bioorganic and bioanalytical chemistry. The vancomycin antibiotics, including vancomycin and ristocetin, are a family of complex glycopeptides which bind specifically to the C-terminal sequence X-D-Ala-D-Ala, where × is L-lysine, L-diaminopimelic acid, L-alanine or L-homoserine. It is shown that non-covalent complexation of vancomycin and ristocetin with peptide ligands in solution, a key molecular recognition phenomenon in antibacterial chemotherapy, can be detected and analyzed in the gas phase by ionspray mass spectrometry. Using Nα,N∊-diacetyl-L-Lys-D-Ala-D-Ala (Ac2KAA) as a representative ligand, it is further demonstrated that correlations of relative ion abundance with ligand concentrations in solution afford a direct method for measuring the binding constants of vancomycin and ristocetin complexes with target peptide sequences in bacterial cell wall. Results for ristocetin-Ac2KAA (Ka = 6.25 × 105 l mol-1) and vancomycin-Ac2KAA (Ka = 7.33 × 105 l mol-1, are in reasonable agreement with previously values [Ka = 5.9 × 105] and 1.5 × 106 l mol-1, respectively).
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jms.1190300509
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