Design of Synthetic Branched Chain Polymeric Polypeptides for Targeting/Delivering Bioactive Molecules

Seymour, L. W.: Passive tumour targeting of soluble macromolecules and drug conjugates. Crit. Rev the Drug. Syst. 9 (1992), 135–162.Google Scholar

Johnson, K. P., Brooks, B. R., Cohen, J. A., Ford, C. C., Goldstein, J., Lisak, R. P., Myers, L. W., Panitch, H. S., Rose, J. W., Schiffer, R. B., Vollmer, T., Weiner, L. P. and Wolinsky, J. S.: Extended use of glatiramer acetate (Copane) is well tolerated and maintains its clinical effect onmultiple sclerosis relapse rate and degreee of disability. Copolymer 1. Multiple Sclerosis Discussion Group. Neurology 50 (1998), 701–708.PubMedGoogle Scholar

Javaherian, K., and McDanal, C.: Random copolymers containing specific ratios of negatively charged and aromatic amino acids bind V3 disulfide loop and neutralize diverse HIV type I isolates. AIDS Res. Hum. Retroviruses 10 (1995) 1163–1168.Google Scholar

Jackson, D.C., O’Brien-Simpson, N., Ede, N.J., and Brown, L.E.: Free radical induced polymerization of synthetic peptides into polymeric immunogens. Vaccine 15 (1997) 1697–1705.CrossRefPubMedGoogle Scholar

Tsikaris, V., Sakarellos, C., Cung, M.T., Marraud, M., and Sakarellos-Daitsiotis, M. Concept and design of a new class of sequential oligopeptide carriers (SOC) for covalent attachment of multiple antigenic peptides. Biopolymers, 381 (1996) 291–293.Google Scholar

Burnham, N.L.: Polymers for delivering peptides and proteins. Am. J. Hosp. Pharm. 51 (1994) 210–218.PubMedGoogle Scholar

Gombotz, W.R., and Pettit, D.K.: Biodegradable polymers for protein and peptide drug delivery. Bioconjugate Chem. 6 (1995) 332–35I.CrossRefGoogle Scholar

Friend, D. R., and Pangburn, S.: Site-specific drug delivery. Medicinal Research Review 7 (1987) 53Google Scholar

Duncan, R.: Drug-polymer conjugates; potential for improved chemotherepy. Anti-Cancer Drugs, 3 (1992) 153–156.Google Scholar

Takakura, Y., and Hashida, M., Macromolecular drug carrier systems in cancer chemotherapy: macromolecular prodrugs. Critical Reviews in Oncology/Haematology 18 (I995) 207–23I.Google Scholar

Maeda, H., Seymour, L.W., and Miyamoto, Y.: Conjugates of anticancer agents and polymers: advantages of macromolecular therapeutics in vivo. Bioconjugate Chem., 3 (1992) 351–362.CrossRefGoogle Scholar

Vasey, P.A., Kaye, S.B., Morrison, R., Twelves, C., Wilson, P., Duncan, R., Thomson, A.H., Murray, L.S., Hilditch, T.E., Murray, T., Burtles, S., Fraier, D., Frigerio, E., and Cassidy, J.: Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin]: first member of a new class of chemotherapeutic agents — drug-polymer conjugates. Clinical Cancer Research 5 (1999) 83–94.PubMedGoogle Scholar

Julyan, P.J., Seymour, L.W., Ferry. D.R., Daryani, S., Boivin, C.M., Doran, J., David, M.. Anderson, D., Christodoulou, C., Young, A.M., Hesslewood, S., and Kerr, D.J.: Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine J. Controlled Release 57 (1999) 281–290.CrossRefGoogle Scholar

Del Giudice, G.: New carriers and adjuvants in the development of vaccines. Current Opinion in Immunology. 4 (1992) 454–459.PubMedGoogle Scholar

Hudecz, F., and Toth, G.K. (1994) Synthetic peptide constructs to increase the immunogenicity of B-cell epitopes, in É. Rajnavolgyi (ed.), Synthetic’ peptides in the search for B-and T-cell epitopes R.G.Landes Company, Austin, pp. 97–119.Google Scholar

Gokulan, K., Khare, S., and Rao, D.N.: Increase in the immunogenicity of HIV peptide antigens by chemical linkage to polytuftsin (TKPR40). DNA Cell Biol. 18 (1999) 623–630.CrossRefPubMedGoogle Scholar

Arnon, R.: Synthetic vaccines based on peptides, oligonucleotides and conjugate anigens. BEHRING Inst. Mitt. 98 (1997) 184–190.PubMedGoogle Scholar

Ben-Yedidia, T., and Arnon, R.: Design of peptide and polypeptide vaccines. Current Opinion in Biotechnology 8 (1997) 442–448.CrossRefPubMedGoogle Scholar

Hudecz, F., Votavova, H., Gaál, D., Sponar, J., Kajtdr, J., Blaha, K., and Szekerke, M. (1985) Branched polypeptides with a poly(L-lysine) backbone: synthesis, conformation and immunomodulation. in Ch.G. Gebelein, and Ch. E. Carraher (eds.) Polymeric, Materials in Medication Plenum Press, New York. pp. 265–289.Google Scholar

Mezo, G., Kajtdr, J., Hudecz, F. and Szekerke, M.: Carrier design: conformational studies of amino acid (X) and oligopeptide (X-DL-Ala,,,) substituted poly[L-lysine]. Biopolymers, 33 (1993) 873–883.PubMedGoogle Scholar

Hudecz, F.: Design of synthetic branched-chain polypeptides as carriers for bioactive molecules. Anti-Cancer-Drugs 6 (1995) 171–193.PubMedGoogle Scholar

Mezo, G., Kajtar, J., Nagy, I., Majer, Zs., Szekerke, M., and Hudecz, F.: Carrier design: Synthesis and conformational studies of poly[L-lysine] based branched polypeptides with hydroxyl groups. Biopolymers 42 (1997) 719–730.Google Scholar

Hudecz, F., Ga, D., Kurucz, I., Ldnyi, S., Kovdcs, A.L., Mezó, G., Rajnavélgyi, E., and Szekerke, M.: Carrier design: cytotoxicity and immunogenicity of synthetic branched polypeptides with poly(L-lysine) backbone. J. Controlled Relase 19 (1992) 231–243.Google Scholar

Clegg, J.A., Hudecz, F., Mezo, G., Pimm, M.V., Szekerke. M., and Baldwin, R.W.: Carrier design: biodistribution of branched polypeptides with poly-(L-lysine) backbone. Bioconjugate Chem., 2 (1990) 425–430.Google Scholar

Hudecz, F. and Szekerke, M.: Investigation of drug-protein interactions and the drug-carrier concept by the use of branched polypeptides as model systems. Synthesis and characterisation of the model peptides. Coll. Czech. Chem. Commun 45 (1980) 933–940.Google Scholar

Sela, M.: (1980) Chemical synthesis for the understanding of immune response phenomena and for their medical application. in C. Larralde, K. Wills, L. Ortiz-Ortiz. and M. Sela (eds.) Molecules, cells, and parasites in immunology Acad Press, New York, pp. 215–228.Google Scholar

Hudecz, F., and Szekerke, M.: Synthesis of new branched polypeptides with poly-lysine backbone. Coll Czech. Chem. Commun., 50 (1985) 103–113.CrossRefGoogle Scholar

Hudecz, F., Kovdcs, P., Kutassi-Kovdcs, S., and Kajtár, J.: GPC, CD and sedimentation analysis of poly-Lys and branched chain poly-Lys-poly-DL-Ala polypeptides. Colloid and Polymer Sci. 262 (1984) 208–212.Google Scholar

Hudecz, F., Kojima, Y., Miyamoto, Y., Kajtzr, J., and Maeda, H.: The effect of charge on the biodistribution of synthetic branched polypeptides in tumour bearing mice. J. Controlled Release 28 (1994) 301–302.CrossRefGoogle Scholar

Pimm, M.V., Clegg, J.A., Hudecz, F., and Baldwin, R.W.: In 111 labelling of branched polypeptide drug carrier with poly[L-lysine] backbone. Int. J. Pharmaceutics 79 (1992) 77–80.CrossRefGoogle Scholar

Idei, M., Dibo, G., Bogd‡n, K., Mezó, G., Horvdth, A,, Erchegyi, J., MészÁros, Gy., Teplán, I., Kéri, Gy., and Hudecz, F.: Analysis of macromolecular branched chain polypeptides by capillary electrophoresis and micellar electrokinetic chromatography. Electrophoresis 17 (1996) 1357–1360.PubMedGoogle Scholar

Hudecz, F., Nagy, I.B., Kóczán, G., Alsina, M.A., and Reig, F. (2000) Carrier design: influence of charge on interaction of branched polymeric polypeptides with phospholipid model membranes. in E. Chiellini (ed.) Frontiers in Biomedical Polymers, Plenum Press, New York, (in press)Google Scholar

Kóczán, Gy., Remenyi, J., Hudecz, F.: Novel RP-HPLC analysis and purification of methotrexate-polymeric branched chain polypeptide conjugates. .J. Chromatography (submitted)Google Scholar

Hudecz, F., Pimm, M.V., Rajnavolgyi, E., Mezó, G., Fabra, A,, Gaá, D., Kovács. A.L., Horváth, A., and Szekerke. M.: Carrier design: New generation of polycationic branched polypeptides containing OH groups with prolonged blood survival and diminished in vitro cytotoxicity. Bioconjugate Chem. 10 (1999) 781–790.CrossRefGoogle Scholar

Marfey. P.: Determination of D-amino acids. II. Use of a bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. Carlsberg Res. Commun. 49 (1984) 591–596.Google Scholar

Szokiin, Gy., Mezo, G., and Hudecz, F.: Application of Marfey’s reagent in racemization studies of amino acids and peptides. J.Chromatography 444 (1988) 115–122.Google Scholar

Votavova, H., Hudecz, F., Kajtár, J., Sponar, J., Blaha, K., and Szekerke, M. f Conformation of branched polypeptides based on poly(L-lysine). Effect of the ionic strength and of the presence of alcohols. Coll. Czech. Chem. Commun. 47 (1982) 3437–3446.Google Scholar

Votavova, H., Hudecz, F., Kajtár, J., Sponar, J., Blaha, K., and Szekerke, M.: Conformation of branched polypeptides based on poly(L-lysine): the effect of terminal amino acids in the branches. Collect. Czech. Chem. Commun. 50 (1985) 228–244.CrossRefGoogle Scholar

Mezo, G., Votavova, H., Hudecz, F., Kajtár, J., Sponar, J., and Szekerke, M.: Conformation of branched polypeptides: The influence of DL-alanine oligomer spacers in the side chains. Coll. Czech Chem. Commun., 53 (1988) 2843–2853.CrossRefGoogle Scholar

Mezo, G., Kajtiir, J., Hudecz, F., and Szekerke, M.: Carrier design: conformational studies of amino acid (X) and oligopeptide (X-DL-Alam) substituted poly[L-lysine] Biopolymers 33 (1993) 873–885.PubMedGoogle Scholar

Nagy, I.B., Haro, I., Alsina, A., Reig, F., and Hudecz, F.: Interaction of branched chain polymeric polypeptides with phospholipid model membranes. Biopolymers 46 (1998) 169–179.CrossRefGoogle Scholar

Goupil, D. W., and Goodrich, F. C.: Interfacial conformational modifictions in a polypeptide. .J. Coll.Interf. Sci. 62 (1977) 142–148.CrossRefGoogle Scholar

Winterhalter, M., Byrner, H., Marzinka, S., Benz, R., and Kasianowicz, J. J.: 1995, Interaction of poly(ethylene-glycols) with air-water interfaces and lipid monolayers: investigation on surface pressure and surface potential. Biophys. J. 69 (1995) 1372–1381.CrossRefPubMedGoogle Scholar

Van Deenen, L. L. M., Demel. R. A., Geurtz van Kessel. W. S. H., Kamp, H. H., Roelfsen, B., Veerkelij, A. J., Wirtz, K. W. A., and Zwall, R. F. A. (1976) in The structural basis of membrane function Y. Hatefi and L. Djavadi-Ohaniance (eds.) Academic Press, New York, pp. 21–38.Google Scholar

Cajal, Y., Alsina, M. A., Rabanal, F., and Reig, F.: A tluorescence and CD study on the interaction of synthetic lipophilic Hepatitis B virus preS(120–145) peptide analogues with phospholipid vesicles. Biopolymers 38 (1996) 607–618.CrossRefPubMedGoogle Scholar

Chu, B.C.F., and Howell, S.B.: Differential toxicity of carrier bound methotrexate toward human lymphocytes,marrow and tumor cells. Biochem. Phamacol. 30 (1981) 2545–2552.Google Scholar

Gaál, D., Hudecz, F., Kov‡fcs, A.L., and Szekerke, M.: Immunomodulatory effect of synthetic branched polypeptides. II. J.Biol.Response Modifiers 5 (1986) 148–159.Google Scholar

Hudecz, F., Kajtár, J., Kurucz, I., Kovács, A.L., and Szekerke, M.: Investigation of the carrier function of polypeptides. Synthesis, conformation and cytotoxicity of oxazolone conjugates of poly(Lys) and poly[Lys-(DL-Alam )]. Makromol. Chem.. Macromol. Symp. 19 (1988) 107–124.Google Scholar

Arnold, L.J. Jr. Gutheil, I., and Kaplan, N.O.: Antineoplastic activity of poly(L-lysine) with some ascites tumor cells. Proc.Natl.Acad. Sci USA 76 (1979) 3246–3250.PubMedGoogle Scholar

Chu, B.C.F.. and Howell, S.B.: Differential toxicity of carrier bound methotrexate toward human lymphocytes,marrow and tumor cells. Biochem Pharmocol. 30 (1981) 2545–2552.CrossRefGoogle Scholar

Rajnavolgyi, E., Hudecz, F., Mezo, G., Szekerke, M., and Gergely, J.: Isotype distribution and fine specificity of the antibody response of inbred mouse strains to four compounds belonging to a new group of synthetic branched polypeptides. Mol Immunol. 23 (1986) 27–37.CrossRefPubMedGoogle Scholar

Gaal, D., Hudecz, F.. and Szekerke, M.: Immunomodulatory effect of synthetic branched polypeptides. I. .J. Biol. Response Modifiers 3 (1984) 174–184.Google Scholar

Bolton, A.E., and Hunter, W.M.: The labelling of proteins to high specific radioactivities by conjugation to a ¹²⁵I-containing acylating agent. Biochem.J. 133 (1973) 529–538.PubMedGoogle Scholar

Pimm, M.V., Gribben, S.J., Mezo, G., and Hudecz, F.: Strategies for labelling branched polypeptides with a poly(L-lysine) backbone with radioiodines (¹²³I, ¹²⁵I, ¹³¹I) and radiometals (¹¹¹In, ⁵¹Cr) for biodistribution studies and radiopharmaceutical development. .J. Labelled Compounds 36 (1995) 157–172.Google Scholar

Pimm. M.V., Perkins, A.C., and Hudecz, F.: Scintigraphic evaluation of the pharmacokinetics of a soluble polymeric drug carrier. Eur.J. Nuclear Medicine 19 (1992) 449–452.Google Scholar

Pimm, M.V., Perkins, A.C., and Hudecz, F.: Gamma scintigraphy for evaluating the biodistribution of synthetic polymeric drug carriers. Nuclear Medicine Communications 13 (1992) 230–231.Google Scholar

Frier, M., Perkins, A.C., Pimm, M.V., and Hudecz, F.: Genetically engineered and synthetic macromolecules as radiopharmaceuticals with potential for liver, lung, blood pool and tumour imaging. Nuclear Medicine Communications 16 (1995) 240–241.Google Scholar

Perkins, A.C., Frier, M., Pimm, M.V., Hudecz, F., and Duncan, R.: Synthetic polymers as potential designer. Eur../. Nucl. Med. 23 (1996) 1134.Google Scholar

Perkins, A.C., Frier, M., Pimm, M.V., and Hudecz, F.: Tc^99m-branched chain polypeptide (BCP): a potential synthetic radiopharmaceutical. J. Labelled Compounds 41 (1998) 631–638.Google Scholar

Hnatowich, D.J., Layne, W.W., Childs, R.L., Lanteigne, D., Davis, M.A., Griffin, T.W., and Doherty, P.W.: Radioactive labeling of antibody: a simple and efficient method. Science, 220 (1983) 613–615.PubMedGoogle Scholar

Hudecz. F., Clegg, J.A., Kajtár, J., Embleton, M.J., Szekerke, M., and Baldwin, R.W.: Synthesis, conformation, biodistribution and in vitro cytotoxicity of daunomycin-branched polypeptide conjugates. Bioconjugate Chem. 3 (1992) 49–57.CrossRefGoogle Scholar

Hudecz, F., Clegg, J.A., Kajtir, J., Embleton, M.J., Pimm, M.V., Szekerke. M., and Baldwin, R.W.: Influence of carrier on biodistribution and in vitro cytotoxicity of methotrexate-branched polypeptide conjugates. Bioconjugate Chem. 4 (1993) 25–33.CrossRefGoogle Scholar

Mezo. G., Mezo, I., Seprodi, A., Teplán, I., Kovács, M., Vincze, B.. Pályi, I., Kajtár, J., Szekerke, M., and Hudecz. F.: Synthesis, conformation, biodistribution and hormon related in vitro anti-tumor effect of a GnRH antagonist-branched polypeptide conjugate. Bioconjugate Chem. 7 (1996) 642–650.CrossRefGoogle Scholar

Pimm, M.V.. Gribben, S.J., Bogd‡n, K., and Hudecz, F.: The effect of charge on the biodistribution in mice of branched polypeptides with poly(L-lysine) backbone labeled with ¹²⁵I, ¹¹¹In or ⁵¹Cr in mice. J Controlled Release 37 (1995) 161–172.CrossRefGoogle Scholar

Vincze, B.. Pdlyi, I., Daubner, D., Kdlnay, A., Mezo, G., Hudecz, F., Szekerke, M.. Teplán, I., and Mezo, I.: Antitumor effect of a GnRH antagonist and its conjugate on human breast cancer cells and their xenografts. .J. Cancer Res. Clin. Oncol. 120 (1994) 578–584.CrossRefPubMedGoogle Scholar

Mezo, G., Mezó, I., Vincze, B., Kálnay, A., and Hudecz, F.: Synthesis and antitumour activity of new GnRH analogue-branched polypeptide conjugates. Cancer Detect.Prev. 22(S) (1998) 239–240Google Scholar

Pató, J., Ulbrich, K., Baker, P., Mezo, G., and Hudecz, F.: Synthesis of macromolecular conjugates of a urokinase inhibitor. J. Bioactive and Compatible Polymers 14 (1999) 99–121.Google Scholar

Mezó, G., Sármay, G., Hudecz, F., Kajtár, J., Nagy, Zs., Gergely, J., and Szekerke, M.: Synthesis and characterization of p-borono-Phe-branched polypeptide-monoclonal antibody ternary systems for potential use in boron neutron capture therapy (BNCT) J. Bioactive and Compatible Polymers 11 (1996) 263–285.Google Scholar

Gaál, D., and Hudecz, F.: Low toxicity and high antitumour activity of daunomycin by conjugation to immunpotential amphoteric branched polypeptide. Eur J. Cancer 34 (1998) 155–161PubMedGoogle Scholar

Hudecz. F.: Alteration of immunogenicity and antibody recognition of B-cell epitopes by synthetic branched polypeptide carriers with poly[L-lysine Backbone. Biomed. Peptides, Proteins and Nucleic. Acids 1 (1995) 213–220.Google Scholar

Garcia, M., Nagy, I.B., Alsina, A., Mezo, G., Reig, F., Hudecz, F., and Haro, I.: Analysis of the interaction with biomembrane models of HAV-VP3(101–121) sequence conjugated to synthetic branched polypeptide carriers with poly[L-lysine] backbone. Langmuir 14 (1998) 1861–1869.CrossRefGoogle Scholar

Sospedra, P., Nagy, I.B., Haro, I., Mestres, C., Hudecz, F., and Reig, F.: Physicochemical behaviour of polylysine[HAV-VP3 peptide] constructs at the air-water interface. Langmuir 15 (1999) 5111–5117.Google Scholar

Nagy, I.B., Alsina, M.A.. Haro, I., Reig, F., and Hudecz, F.: Phospholipid — model membrane interactions with branched polypeptide conjugates of a hepatitis a virus peptide epitope. Bioconjugate Chemistry. 11 (2000) 30–38.CrossRefPubMedGoogle Scholar

Hudecz, F., Hilbert, Á., Mezo, G., Mucsi, I., Kajtár, J. Bósze, Sz., Kurucz, I., and Rajnavolgyi, E. (1994) The use of branched polypeptide carrier based conjugates for the design of synthetic vaccine against HSV infection. in R. Epton (ed.) Innovation and Perspectives in Solid Phase Synthesis — Peptides, Polypeptides and Oligonucleotides — 1994 Intercept, Andover, pp. 315–320.Google Scholar

Hudecz, F., Hilbert, Á, Mezó, G., Kajtiir, J. and Rajnavolgyi, E.: B-cell epitopes in Herpes simplex Virus-(HSV-1) glycoprotein D (gD). In Synthetic peptides in the search for B-and T-cell epitopes. (Rajnavolgyi, E. ed.) R.G.Landes Company, Austin, pp. 157–169., 1994.Google Scholar

Venkataprasad, N., Coombes, A.G.A., Singh, M., Rhode, M., Wilkinson, K.A., Davies, S.S., Hudecz, F., and Vordermeier, M.H.: Resorbable lamellar subtrates of lactide polymers induce potent cellular immunity to an adsorbed mycobacterial antigen. Vaccine, 17 (1999) 1814–1819.CrossRefPubMedGoogle Scholar

Wilkinson, K.A., Hudecz, F., Vordermeier, H.M., Ivanyi, J., and Wilkinson R.J.: Enhancement of the T cell response to a mycobacterial peptide by conjugation to synthetic branched polypeptide Eur. J.Immunol. 29 (1999) 2788–2796.CrossRefPubMedGoogle Scholar

Wilkinson, K.A., Vordermeier, M.H., Wilkinson, R., Ivanyi, J. and Hudecz, F.: Synthesis and in vitro T cell immunogenicity of conjugates with dual specificities: attachment of epitope peptides of I6 kDa and 38 kDa proteins from M.tuberculosis to branched polypeptide. Bioconjugate Chem., 9 (1998) 539–547.CrossRefGoogle Scholar