Vancomycin-peptide complex

Figure 3.23. Vancomycin-peptide complex used by Williams et al. (311-315) to investigate components of free energy of binding.

For example, Williams (311-314) used a vancomycin-peptide complex (Fig. 3.23) as an experimental system in which to evaluate the various contributions to binding affinity. A similar analysis for antibody mutants was attempted by Novotny (262). 

Example Vancomycin-peptide complex Williams et al. (1992) made use of a vancomycin-peptide complex to demonstrate evidently the precise and exact evaluation of the different aspects of contributions to the ensuing binding affinity in an experimental measurement, as depicted in Figure 3.7. 

FIGURE 7.17 Fluorescence lifetime temperature measurements for gas-phase biomolecular ions of (a) Trp-cage protein charge states (b) Dye-(Pro) -Arg-Trp peptide sequences, [M -H H] (c) Vancomycin-peptide non-covalent complexes, [M H- H] +. Best-fits for the quenching rate model are shown by lines through each set of data points. 

Berthod et al. also tried copper complexation with teicoplanin and TAG CSPs [19]. Similar results were obtained. Amino acid enantiomers perfectly separated by both teicoplanin and TAG CSP could no longer be separated as soon as copper was present in the mobile phase. The copper-teicoplanin complex is also formed with the primary amine group on the peptidic teicoplanin basket (Figs. 1 and 3). However, unlike the vancomycin-copper complex which was very stable [18], the teicoplanin-copper complex was found to be reversible. Indeed, amino acid enan-tioselectivity was mostly restored after washing the chiral column with several column volumes of copper-free clean mobile phase [19]. 

The glycopeptide antibiotics such as vancomycin and chloroeremomycin are complex nonribosomal peptides. One of the nonprotein amino acids found in these antibiotics is 4-hydroxyphenylglycine. The biosynthetic pathway of this nonprotein amino acid has been studied and prephenate was... 

Jorgensen, T. J. D., Hvelplund, P., Andersen, J. U., Roepstorff, P. Tandem mass spectrometry of specific vs. nonspecific noncovalent complexes of vancomycin antibiotics and peptide ligands. Int J Mass Spectrom 2002, 219, 659-670. Tahallah, N., Pinkse, M., Maier, C. S., Heck, A. J. The effect of the source pressure on the abundance of ions of noncovalent protein assemblies in an electrospray ionization orthogonal time-of-fiight instrument. Rapid... 

A final example of metabolic pathway engineering is based on polyketide and nonribosomal peptide biosynthesis. Polyketides and nonribosomal peptides are complex natural products with numerous chiral centers, which are of substantial economic benefit as pharmaceuticals. These natural products function as antibiotics [erythromycin A (65), vancomycin (66)], antifungals (rapamycin, amphotericin B), antiparasitics [avermectin Ala (67)], antitumor agents [epothiolone A (68), calicheamicin yj, and immunosuppressants [FK506 (69), cyclosporin A], Because this exponentially growing and intensely researched field has developed, the reader is directed to review articles for additional details.347-359 Also with the potential economic benefit to develop the next blockbuster pharmaceutical, a number of patents and patent applications have been published.360-366... 

For example, proteinogenic and non-proteinogerhc amino acids in l- and n-config-uration are assembled in non-ribosomal peptides. (3) Decorating enzymes can add sugar moieties to the peptide or polyketide backbone resulting in complex structures like the glycosylated antibiotic vancomycin. 

Jorgensen, T.J.D. Roepstorff, P Heck, A.J.R. Direct Determination of Solution Binding Constants for Noncovalent Complexes Between Bacterial Cell Wall Peptide Analogs and Vancomycin Group Antibiotics by Electrospray Ionization Mass Spectrometry, AnaZ. Chem. IQ, 4427 432 (1998). 

To date, the capability of macromolecular peptides as molecular recognition sites has been poorly characterized. Due to the analytical techniques available, first investigations on host-guest complexes were done in the homogeneous phase [55]. One of the most popular cyclic compounds is the depsipeptide, valinomycin, which can complex potassium ions selectively and carry them through lipid membranes [56], Another interesting receptor is the peptide antibiotic, vancomycin [57], This consists of a complicated tricyclic pep-tidic structure and can be used as chiral selector [58] in capillary electrophoresis and HPLC. 

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