Conjugated terthiophene and furan compounds with photoenhanced b

Details Conjugated terthiophene and furan compounds with photoenhanced b Conjugated terthiophene and furan compounds with photoenhanced b

1996-11-22

1999-02-09

Feisee, Lila

Drug, bio-affecting and body treating compositions

Conjugate or complex of monoclonal or polyclonal antibody,...

Conjugated via claimed linking group, bond, chelating agent,...

4241791, 424 153, 5303917, 536115, 536118, 540 1, 435 721, A61K 39395, A61K 3940, C07K 1600, C07H 1100

Patent

active

058690514

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention concernes conjugates consisting of a carrier molecule linked to an organic molecule able to efficiently produce singlet oxygen after irradiation suitably derivatized as to react with an amino or thiol group of the carrier molecule. Said conjugates are able to work out a biocidal action on various kinds of cells, either in vivo or in vitro, once activated with radiations in the near UV; they may be used either for therapeutical or diagnostic aim.


PRIOR ART

It is known that organic molecules, able to efficiently produce singlet oxygen as a result of irradiation, have photoenhanced biocidal activity. The biocidal activity of the molecules shows itself against essentially every living form such as viruses, fungi, bacteria, invertebrates, 181 (1991); J. B. Hudson et al.: Chemosphere 19, 1329 (1989); J. B. Hudson et al.: Chemosphere 18, 2317 (1989)!.
The biocidal properties make these molecules extremely interesting for a great number of applications in therapy. However the practical application of the above mentioned molecules is strongly limited because they are powerful contact allergens and cause, once administered and irradiated, erythemas, pruritus and hyperpigmentation for periods of weeks and months et al.: J. Invest. Dermatol. 87, 354 (1986)!. It is thus obvious the interest to develop compounds which, while keeping the desired biocidal capabilities, do not show the undesirable side effects.


DETAILED DESCRIPTION OF THE INVENTION

Now it has been surprisingly discovered that it is possible to remove the negative effects related to the use of the above mentioned molecules keeping unaltered their biocidal properties by conjugating the organic molecule able to produce efficiently singlet oxygen after irradiation to a carrier molecule able to direct it on a definite biological target.
According to a particular embodiment of the present invention the organic molecule able to produce efficiently singlet oxygen after irradiation is a molecule having general formula (I) ##STR1## wherein Z.sub.1, Z.sub.2, Z.sub.3 equal or different one another are S or O, suitably derivatized as to react with an amino or thiol group of the carrier molecule.
According to a further particular embodiment of the invention the organic molecule able to produce efficiently singlet oxygen as a result of irradiation is the 2,2':5',2"-terthiophene (hereinafter abbreviated as .alpha.-T) molecule having formula (I) in which Z.sub.1 .dbd.Z.sub.2 .dbd.Z.sub.3 .dbd.S.
According to the invention the carrier molecule is selected from the group consisting of: antibodies (native, monoclonal or recombinant) peptides, haptamers (nucleic acids with the capability of a selective bond toward a target), sugars, or other analogous carriers able to direct the derivative having formula (I) toward a biological target as for example the avidin-biotin conjugate.
In particular the terthienyl compound may be derivatized with a group able to react with amino groups (for example side chains of lysine residues in peptides or proteins), with thiol groups (for example side chains of cysteine), with suitably modified saccharide residues of the carrier molecule or with avidin and/or biotin utilizing the functional groups present in these molecules; these solutions allow to conjugate the terthienyl derivative with a wide spectrum of different molecules.
The derivatization of the terthienyl compound is carried out preferably in position 2.
When the terthienyl derivative is linked to Avidin and/or Biotin the conjugate object of the present invention may be directly formed in vivo separately administering the part formed by Biotin bound to the carrier molecule and the part formed by Avidin bound to the .alpha.-T derivative or vice versa.
The utility of these systems consists in the fact that they allow the administration of an inferior quantity of the .alpha.-T derivative without lowering the potential therapeutic efficiency of the molecule, making it available various .alpha.-T derivatives conjugated both to Biotin and Av

REFERENCES:
J. Invest. Dermatol., vol. 87, No. 3, 354-357, Aug. 1986.
Spikes et al., Chemical Abstract, vol. 118, No. 25, Jun. 21, 1993.
Mares et al., Chemical Abstract, vol. 123, No. 1, Jul. 3, 1995.
Klyashchitsky et al., J. Controlled Release, vol.29, 1-16, 1994.
Hudson et al., Chemical Abstract, vol. 119, No. 23, Dec. 6, 1993.
Hudson, J.B., et al, "Photoactive Antiviral and Cytotoxic Activities of Synthetic Thiophenes and Their Acetylenic Derivatives," Chemosphere, vol. 19 (1989), No. 8/9, pp. 1329-1343.
Hudson, J.B., et al, "Therapeutic Potential of Plant Photosensitizers," Pharmac. Ther., vol. 49 (1991), pp. 181-222.
Hudson, J.B., et al, "Ultraviolet-Mediated Antibiotic Activity of Synthetic Thiophenes and Their Acetylenic Derivatives," vol. 18 (1989), Nos. 11/12, pp. 2317-2327.
Lavoie, Thomas B., et al., "Experimental Analysis by Site-Directed Mutagenesis of Somatic Mutation Effects on Affinity and Fine Specificity in Antibodies Specific for Lysonzyme," vol. 148, No. 2, Jan. 15, 1992, pp. 503-513.
Natali, P.G., et al, "Phenotyping of Lesions of Melanocyte Origin With Monoclonal Antibodies to Melanoma-Associated Antigens and to HLA Antigens," JNCI, vol. 73, No. 1, Hul. 1984, pp. 13-18.
Neri, Dario et al, "High-affinity Antigen Binding by Chelating Recombinant Antibodies (CRAbs)," J. Mol. Biol., No. 246, (1995), pp. 365-373.
Winter, Greg, et al, "Man-made Antibodies," Nature, vol. 349, Jan. 24, 1991, pp. 293-299.
Berzofsky et al. Fundamental Immunology (W.E. Paul, ed.) Raven Press; Ch. 8, 1993.
Boch et al. Photochem. Photobiol. 59:875, May 1994.
Boch et al. Photochem. Photobiol. 64(1):92-99, 1996.
Ghose et al. Meth. Enzymol. 93:280-333, 1983.
Hudson et al. Photochem. Photobiol. 44(4):477-82, 1986.
Hudson et al. Chemosphere 19(8/9):1329-43, 1989.
MacEachern et al. Tetrahedron 44(9):2403-12, 1988.
Marles et al. Photochem. Photobiol 55(4):479-87, 1992.
Rossi et al. Tetrahedron 47(39):8443-60, 1991.

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