Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Cyclic peptides
Patent
1997-12-18
1999-08-17
Tsang, Cecilia J.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
Cyclic peptides
514 8, 514 9, 514 11, A61K 3814, C07K 900
Patent
active
059395230
DESCRIPTION:
BRIEF SUMMARY
The present invention refers to a method for purifying antibiotic compounds of the dalbaheptide family by means of an electrophoretic technique known as isoelectric focusing.
More precisely, the present purification method refers to isoelectric focusing (IEF) of dalbaheptide antibiotics in a multicompartment electrolyzer with IMMOBILINE membranes, in particular zwitterionic membranes.
A further object of the invention are pure antibiotic compounds obtainable according to the present process, in particular the pure 6.sup.B-decarboxy- 6.sup.B-(hydroxymethyl)-N.sup.63 -3-(dimethylamino)propyl amide derivative of antibiotic A40926.
A thorough description of the principles and methods of IEF in multicompartment electrolyzer with IMMOBILINE membranes can be found in ref. 5.
According to this technique, the compound to be purified is an amphoteric substance characterized by having a determined isoelectric point (pI), and good buffering properties at the pI value (see ref. 102). The mixture to be purified is contained in a liquid vein and it is trapped into one of a set of chambers, said chamber being delimited by two IMMOBILINE membranes having isoelectric points encompassing the pI of the desired compound. Thus, by a continuing electrophoretic titration process, all other impurities, either non-isoelectric or with different pI values are forced to leave the chamber, towards more anodic or cathodic chambers, while the purified compound is left into the initial chamber.
This purification technique has been applied to a number of proteins such as eglin C (ref. 5), monoclonal antibodies against the gp-41 of the AIDS virus (ref. 103), recombinant human growth hormone (ref. 104), the epidermial growth factor receptor (refs. 105 and 106), recombinant superoxide dismutase (ref. 107), interleukin (ref. 108) and glucoamylase (ref. 109).
The present invention discloses for the first time a suitable methodology for applying such IEF purification technique to rather small molecules, with a molecular weight of about 1800 daltons, and specifically to the antibiotic compounds of the dalbaheptides family.
With the term dalbaheptides are usually defined all antibiotic substances having in common a highly modified linear heptapeptidic structure made up of seven amino acids, five of which are constantly aryl- and arylmethyl-amino acids, said structure being determinant of a common mechanism of action, i.e. the specific complexation with the D-alanyl-D-alanine terminus of one or more intermediates of the cell wall synthesis which leads to cell disruption. The term dalbaheptide thus derives from the wording D-al{anyl-D-alanine} b{inding} a{ntibiotics} {having} hept{apept}ide {structure}.
The dalbaheptide antibiotics can conventionally be represented by the following general formula I ##STR1## wherein: W, Z, X.sub.1, X.sub.2 and T represent the relative portions of an antibiotic of the dalbaheptide group; and Y represents a carboxyacid group or a functional derivative thereof.
The formula I includes the salts of dalbaheptide antibiotics with acids and bases as well as their inner salts.
In the general structure represented by the formula I, the above mentioned five fundamental aryl- and arylmethylaminoacids are those connected with the moieties Z and W. Apart from slight differences in the substitutions on the respective aryl portion, the five aryl- and arylmethyl aminoacids are substantially common to all members of the dalbaheptide antibiotics group, while the different type and structure of the two remaining aminoacid portions which bear the substituents X.sub.1 and X.sub.2 allow a further classification of the dalbaheptides so far known into four different sub-groups, each of which is referred, for practical reasons, to a well known antibiotic of the group that, in the previous scientific literature, has been generally identified as glycopeptide antibiotics.
Said four sub-groups can be defined respectively as ristocetin-type, vancomycin-type, avoparcin-type and synmonicin-type antibiotics.
For a detailed classification of the dalb
REFERENCES:
patent: 2951766 (1960-09-01), White
patent: 4322343 (1982-03-01), Debono
patent: 4504467 (1985-03-01), Molloy et al.
patent: 4521335 (1985-06-01), Chan et al.
patent: 4552701 (1985-11-01), Nagarajan et al.
patent: 4563442 (1986-01-01), Clem et al.
patent: 4639433 (1987-01-01), Hunt et al.
patent: 4643987 (1987-02-01), Nagarajan et al.
patent: 4698327 (1987-10-01), Nagarajan et al.
patent: 4742045 (1988-05-01), Verma et al.
patent: 4782042 (1988-11-01), Selva et al.
patent: 4804534 (1989-02-01), Riva et al.
patent: 4868171 (1989-09-01), Selva et al.
patent: 4882313 (1989-11-01), Sitrin
patent: 4935238 (1990-06-01), Selva et al.
patent: 4954482 (1990-09-01), Maeda et al.
patent: 4954483 (1990-09-01), Malabarba et al.
patent: 4971670 (1990-11-01), Faupel et al.
patent: 5064811 (1991-11-01), Borghi et al.
patent: 5185320 (1993-02-01), Trani et al.
patent: 5194424 (1993-03-01), Malabarba et al.
Sitrin et al, Journal of Antibiotics, vol. 37, No. 11, pp. 1475-1478, Nov. 1984.
Bossi et al, Electrophoresis, vol. 17, (7), pp. 1234-1241, 1966.
Malabarba et al, J. Antibiotics, vol. 40, No. 11, (Nov. 1987) pp. 1572-1587.
Gauze, G.F., et al, Eremomycin, a novel cyclic glycopeptide antibiotic. Antibiot. Med. Biotecknol. 1987; 32: 571-576 (English Translation).
Berdnikova, T.F. et al, Structure of the aglycone of eremomycin, a novel antibiotic of the group of polycyclic glycopeptides. Antibiot. Kimioter. 1988; 33: 566-570 (English Translation).
Lomakina, N.N., et al, Structure of eremosamine, an amigo sugar from eremomycin. Antibiot. Kimioter. 1988; 33: 726-729 (English Translation).
Parenti et al, Drugs of the future, vol. 15(1), pp. 57-72, (1990).
Cavalleri et al, "Glycopeptides (dalbaheptides)", Kirk-Othmer's Encyclopedia of Chemical Technology, vol. 2, pp. 995-1018, J. Wiley & Sons, 1992.
Sztaricskai et al, The Chemistry of the Vancomycin Group of Antibiotics. In: Recent Developments in the Chemistry of Natural Carbon Compounds, vol. X. R. Bogner and Cs. Szantay (Eds.). Akademiai Kaido 1984; pp. 91-201.
Righetti et al, J. Chromatogr. 475, pp. 293-309 (1989).
Williams, D.H., et al, Structure of the antibiotic ristocetin A.J.C.S. Chem. Comm. 1979: 906-908.
Debono, M. et al, Actaplanin, new glycopeptide antibiotics produced by Actinoplanes missouriensis. The isolation and preliminary chemical characterization of actaplanin, J. Antiboit. 1984; 37: 85-95.
Hunt, A.H.. et al, Structures of the actaplanins. J. Org. Chem. 1984; 49: 641-645.
Borghi, A., et al, Teichomycins, new antibiotics from Actinoplanes teichomycetius nov.sp.IV. Separation and characterization of the components of teichomycin (teicoplanin). J. Antibiot. 1984; 37: 615-626.
Coronelli, C., et al, Teicoplanin: chemical physico-chemical and biological aspects. Farm Ed. Sci. 1987; 42: 767-786.
Barna, J.C.J, et al, Structure elucidation of the teicoplanin antibiotics. J. Am. Chem. Soc. 1984; 106: 4895-4902.
Michel, K.H., et al, A35512, a complex of new antibacterial antibiotics produced by Streptomyces cadnidus. I. Isolation and Characterization. J. Antibiot. 1989; 33: 1397-1406.
Harris, C.M., et al Structural studies of glycopeptide antibiotic A35512B. Identification of the diphenyl ether-type bis (amino acid). Tetrahedron 1983; 39: 1661-1666.
Eggert, J.H., et al, A41030, a complex of novel glycopeptide antibiotics. Discovery, fermentaiton, isolation and characterization. 23rd Intersci. Conf. Antimicrob. Agents Chemother (Oct 24-26, Las Vegas) 1983; Abst. 440.
Hunt, A.H. et al, Structure of Antibiotic A41030A, J. Org. Chem. 1985; 50: 2031-2035.
Boeck, L.D., et al, A47934, a novel glycopeptide-aglycone antibiotic produced by a strain of Streptomyces toyocaensis. Taxonomy and fermentation studies. J. Antibiot. 1986; 39: 1533-1540.
Hunt, A.H., et al, A47934 and A41030 factors-new glycopeptides and glycopeptide aglycones: structure determination. 32rd Intersci. Conf. Antimicrob. Agents Chemother. (Oct. 24-26, Las Vegas) 1983; Abst. 441.
Sitrin, R.D, et al, Aridicins, novel glycopeptide antibiotics. II. Is
Bossi Alessandra Maria
Righetti Pier Giorgio
Riva Ernesto
Zerilli Luigi Franco
Gruppo Lepetit SpA
Homan Ruth E.
Tsang Cecilia J.
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