Vancomycins

For this review we have selected the cyclic modified peptides mentioned above, i.e. vancomycin, nisin, cyclosporin, and cyclotheonamide, as well as two examples, i.e. RGD-containing cyclic peptides and SH2 domain binding cyclic peptides, which were inspired by proteins. 

Dimerization of vancomycin and other glycopeptide antibiotics, as well as anchoring of glycopeptides in the bacterial cell membrane, contribute favorably to the 

Although the total syntheses of vancomycin and derivatives can be heralded as top achievements in organic synthesis [1], they are of course not practical for obtaining these compounds for application purposes. Therefore, there has been considerable interest in the preparation of simplified mimics of vancomycin, having especially (part of) the binding cavity for D-Ala-D-Ala. 

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Vancide 89RE Vancide TH Vancide 51Z Vancocin Vancomycin... 

The chirobiotic chiral stationary phases (103,104) are based on macrocycHc antibiotics such as vancomycin (4) and teicoplanin (5). 

A51568A (A/-demethyl-vancomycin), B Nocardia orientalis N RRL 15232 1982 Lilly 39,40... 

Table 4. Naturally Occurring Vancomycin-type Dalbaheptides...

Other specific discovery assays have been used such as differential inhibition of a vancomycin resistant S. aureus strain and its susceptible parent, and an assay based on antagonism of the antibacterial activity by N,A/-diacetyl-L-Lys-D-Ala-D-Ala [24570-39-6] a tripeptide analogue of the dalbaheptides receptor. AppHcation of this latter test to 1936 cultures (90) led to the isolation of 42 dalbaheptides, six of which, including kibdelin (Table 3), parvodicin (Table 3), and actinoidin A2 (68) were novel. A colorimetric assay based on competition between horseradish peroxidase bound teicoplanin and the... 

Biosynthesis. Biochemical studies on dalbaheptides have been reviewed (92,97). Experiments with and H have shown that in vancomycin (39), D-tyrosine is the precursor of D-/> -hydroxyphenyiglycine and P-hydroxy-y -chlorotyrosine, and acetate the precursor of the two y jy -dihydroxyphenyiglycines (98). Similar results using either or radioactively labeled material have been reported for avoparcin (Table 5) (23), ristocetin (Table 2) (99,100), ardacin (Table 3) (101), and A47934 (102). 

In Vitro Properties. The antibacterial spectmm of most dalbaheptides is known (Table 1). Vancomycin (39) and/or teicoplanin (Table 3) are generally introduced as reference compounds. Direct comparative data for some dalbaheptides tested under the same experimental conditions are given in... 

In Vivo Properties. The efficacy of dalbaheptides has been assessed ia various models of experimental septicemia ia mice. In general there was good correlation between the ED qS (effective doses which prevent death ia 50% of test animals) and the MICs on test strains. Teicoplanin was very effective, ED q values ranged from 0.11 to 0.72 mg/kg sc administration for septicemias caused by S. pyogenes S. pneumoniae and S. aureu whereas for vancomycin ED qS were from 0.58 to 7.2 mg/kg (33). Eremomycin (52) had therapeutic activity 2—3 times greater than vancomycin. Therapeutic indices... 

This resistance, inducible by low concentrations of dalbaheptides, is plasmid mediated and is transferable. Concomitant with the induction of resistance is the appearance or increased expression of a protein having a molecular weight of either 39,500 or 39,000. The enzymatic activity of this material has been postulated (112). Although the mechanism of resistance induction by dalbaheptides is unknown, different dalhabaheptides have different induction capacity. Vancomycin (39) is the most powerful inducer teicoplanin is a very weak inducer. 

Only three dalbaheptides are commercialized vancomycin (39) and teicoplanin (18—22) for human health, and avoparcin (63—65) for animal usage. Vancomycin, the main trademark of which is EH Lilly s Vancocin had 1990 sales around 160 million. Total annual production is in the vicinity of 8 t. Teicoplanin, trademarked Targocid, had 1990 sales of 35 million corresponding to 200 kg. Teicoplanin is commercialized in Europe, Hong Kong, Korea, and the Middle East. It is at the late developmental clinical phase in North America and Japan. Avoparcin is used as a growth promoting feed additive (see... 

Clinical Use. Vancomycin and teicoplanin as fomiulated dmgs are lyophilized powders to be reconstituted with sterile water for injection. Vancomycin hydrochloride [1404-93-9] is presented in vials of 500 mg that give 100—200 mL solution of pH 2.5—4.2. It is administered by slow (60 min) infusion at a dose of 500 mg every 6 h or 1 g every 12 h/d. The teicoplanin contains the five factors (87%) plus 13% of the pseudoaglycone T-A3-1. It is presented in vials containing 200 mg of lyophili ed power that after dissolution with 3 mL of solvent gives a solution at pH 7.5. The dose regimen is 200—800 mg/d by iv bolus adrninistration. 

The column was 25 cm long, 4.6 mm I.D. and packed with Partisil 10. It is seen that linear curves were obtained for three different solutes and two different moderators in n-heptane. Scott and Beesley [14] obtained retention data for the two enantiomers, (S) and (R) 4-benzyl-2-oxazolidinone. The column chosen was 25 cm long, 4.6 mm I.D. packed with 5 mm silica particles bonded with the stationary phase Vancomycin (Chirobiotic V provided by Advanced Separations Technology Inc., Whippany, New Jersey). This stationary phase is a macrocyclic glycopeptide Vancomycin that has a molecular weight of 1449.22, and an elemental composition of 54.69% carbon. 

Chemistry, biology, and medicine of glycopeptide antibiotics, in particular synthesis of vancomycin 99AG(E)2096. 

Vancomycin group of antibiotics and the fight against resistant bacteria 99AG(E)1172. 

Studies on the synthesis of vancomycin and related cyclic peptides 98PAC391. 

Zhn and coworkers have developed SwAr-based macrocyclizadon via biaryl ether formation. The first example of SivAr-based macrocyclizadon for synthesis of model carboxylate-binding pocket C-O-D rings of vancomycin was reported in 1994 fScheme 9.3. ... 

Double intramolecular S Ai reaction leads to a model bicyclic C-O-D-O-E ring, as shown in Eq 9 9 " Synthesis of a model 22-membered AEl-C-0-D ring of vancomycin using similar strategy has been reported Totiil synthesis of vancomycin has been accomplished by Nicolaon and coworkers ... 

The medium is placed in a container having a suitable excess capacity in order to insure the presence of sufficient oxygen and is sterilized by heating at 120°C for about 30 minutes. When cool, the medium is inoculated with about 25 ml of a vegetative inoculum as described above, and the culture is then shaken for about 80 hours at 26°C. The pH of the medium at the beginning of fermentation ranges from about 6.5 to about 7.0 and the final pH is about 7.0 to about 8.0. A fermentation broth thus obtained contained about 180 m9 of vancomycin per ml. 

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