Vancomycin derivatives

Leadbetter MR, Adams SM, Bazzini B, Fatheree PR, Karr DE, Krause KM, Lam BM, Linsell MS, Nodwell MB, Pace JL, Quasi K, Shaw JP, Soriano E, Trapp SG Villena JD, Wu TX, Christensen BG Judice JK. (2004) Hydrophobic vancomycin derivatives with improved ADME properties Discovery of telavancin (TD-6424). J Antibiot 57 326-336. 

Because of the ultimate importance of vancomycin in the treatment of often fatal infections caused by multiple-resistant bacteria, extensive efforts have been directed toward the discovery of vancomycin derivatives with activity against these drug-resistant bacteria [89]. As a result of these efforts, several derivatives such as 41 (LY264826) have been found to be up to 500 times more effective than vancomycin itself. The most notable difference is the presence of another... 

To this triacetylated vancomycin derivative (10 mg, 0.005 mmol) in dry MeOH (0.5 mL) was added K2C03 (3 mg, 0.02 mmol) and the mixture was stirred for 4h. This was filtered and the solvent was removed. The residue was purified by preparative TLC (silica gel, MeOH/CH2Cl21 1) to give AW-di-Z vancomycin methyl ester yield 8mg (95%). 

Ge M, Chen Z, Onishi HR et al (1999) Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding D-Ala-D-Ala. Science 284 507-511... 

Mehlmann, M., Garvin, A. M., Steinwand, M., Gauglitz, G. (2005). Reflectometric interference spectroscopy combined with MALDI-TOF mass spectrometry to determine quantitative and qualitative binding of mixtures of vancomycin derivatives. Anal. 

Figure 7 Localization of cell wall synthesis in isogenic pairs of vancomycin-susceptible and vancomycin-resistant Staphylococcus aureus strains. Images show labeling of JH1/JH9 (susceptible) and COL/VM50 (resistant) cells with a fluorescent vancomycin derivative, after growth with an excess of o-serine (synthesis of older peptidoglycan with D-Ala-D-ser termini, to which the labeled vancomycin cannot bind) followed by transient incubation with o-Alanine, which results in n-Ala incorporation into new peptidoglycan, to which the vancomycin can bind. In all cases, the main location for cell wall synthesis is at the division septum. Data reproduced from P. M. Pereira S. R. Filipe A. Tomasz M. G. Pinho, Antimicrob. Agents Chemother. 2007, 51 (10), 3627, with permission from the American Society for Microbiology.

M.C. Lawson, R. Shoemaker, K.B. Hoth, C.N. Bowman, K.S. Anseth, Polymerizable vancomycin derivatives for bactericidal biomaterial surface modification structure—function evaluation. Biomacromolecules 10 (2009) 2221-2234. 

In Denmark, there were in 1994 some 24 tonnes of vancomycin derivatives used in animal health, and only 24 kilograms for the treatment of human diseases. Later, the Danish Government prohibited the use of vancomycin derivatives as feedstock additives the European Union followed suit in 1998. All classes of antibiotics, which find use in human medicine, are no longer allowed as growth promoters in livestock. 

Scheme 11. Dimerization of vancomycin derivatives through cross-metathesis. (Nicolaou et al., 2000) ...

A chloro biphenyl vancomycin derivative that has Considerably higher potency than vancomycin it is curremly undergoing testing by Ell Lilly as a vancomycin alternative see Chapter 12. 

An alternative approach to enhancing activity of vancomycin-1 ike glycopeptides is under study by Griffin and colleagues (127). The overall objective is eventually to build a molecule that will have catalytic as well as binding activity. Vancomycin derivatives... 

Synthesis of a multivalent vancomycin derivative exhibiting significantly enhanced antibacterial activity against vancomycin-resistant enterococi has been recently reported (94). This work was built upon the finding that dimeric vancomycin showed enhanced affinity toward the L-lysyl-D-alanyl-D-alanine peptido-glycan precursor that is responsible for the growth of the bacterial cell wall (95). A... 

Polymerizable Vancomycin Derivatives for Bactericidal Biomaterial Surface Modification Structure-Function Evaluation, 2009, 10,... 

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