Poly-L-glutamic acid conjugates

N. Nishigori, Y. Suzuki, O. Kanie, C.-H. Wong, A lysoganglioside poly-L-glutamic acid conjugate as a picomolar inhibitor of influenza hemagglutinin, Angew. Chem., Int. 

Li C, Ke S, Wu QP, Tansey W, Hunter N, Buchmiller LM, Milas L, Chamsangavej C, Wallace S. Tumor irradiation enhances the tumor-specific distribution of poly(L-glutamic acid)-conjugated paclitaxel and its antitumor efficacy. Clin Cancer Res 2000 6 2829-2834. 

Bhatt, R. L., de Vries, E,Tulinsky, J, Bellamy, G., Baker, B., Singer, J. W. and Klein, P. (2003) Synthesis and in vivo antitumor activity of poly(L-glutamic acid) conjugates of 20(S)-camptothecin. J Med Chem, 46,190-193. 

Kamiya, S. Kobayashi, K. (1998). Synthesis and helix formation of saccharide-poly(L-glutamic acid) conjugates. Macrornoi. Chem. Phys., 199, 1589-1596. 

Li, C. Poly(L-glutamic acid)-anticancer drug conjugates. Adv. Drug Del. Rev. 54 695, 2002. 

Bhatt [3] prepared antineoplastic agents consisting of poly-L-glutamic acid— camptothecin conjugates, (III) and (IV), as a method for improving the limited solubility of 20(S)-camptothecin and analogues in aqueous medium. 

Li, C. Yu, D.-R Newman, R. A. Cabral, P. Stephens, L. C. Milas, L. Wallace, S. Complete regression of well-established tumors using a novel water-soluble poly(L-glutamic acid)-paclitaxel conjugate. Cancer Res., 1998, 58 2404—2409. 

With respect to the advantage of using a protein rather than a synthetic polypeptide as a carrier, we can refer to Jaffe et who showed that an active fragment of gastrin, its C-terminal tetrapeptide amide, was antigenic when covalently attached to serum protein carriers but not when linked to poly(L-lysine) or to poly(L-glutamic acid). Walker et al. in 1973 made similar comparisons with steroid conjugates and obtained the same result, i.e., bovine serum albumin was a better carrier than poly(L-lysine). (But also see below. 

Tsukada Y, Kato Y, Umemoto N, Takeda Y, Kara T, Hirai H. An anti-oc-fetoprotein antibody-daunorubicin conjugate with a novel poly-L-glutamic acid derivative as intermediate drug carrier. J Natl Cancer Inst 73 1984 721-729. 

Fig. 2 Chemical structures of a bifunctional poly(L-glutamic acid)-(Gd-D03A)-mesochlorin eg conjugate (A) and its pegylated bifunctional conjugate (B)...

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