title: Modification of cyclosporin A and conjugation of its derivative to HPMA copolymers.
abstract: Cyclosporin A (CsA) was epoxidized with m-chloroperoxybenzoic acid in the presence of sodium carbonate or with tert-butyl hydroperoxide in the presence of dioxomolybdenum iminodiethanoxide. The CsA epoxide was not stable and rearranged into a compound with a more stable five-member ring structure. An amino group containing cyclosporin A derivative (CsA amine) was obtained by the reaction of CsA epoxide with excess ethylenediamine. The yield of the CsA amine was 30--40% based on the CsA. An HPMA copolymer--CsA conjugate was prepared by the reaction of the CsA amine with an HPMA and MA-Gly-Phe-Leu-Gly-ONp copolymer. The content of CsA amine in the conjugate was 8.7 wt %. The CsA amine was released from the copolymer by enzymatic hydrolysis with papain.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Lu
authors.forename: S Q
authors.initials: SQ
authors.lastname: Gao
authors.forename: P
authors.initials: P
authors.lastname: Kopecková
authors.forename: J
authors.initials: J
authors.lastname: Kopecek
mesh_terms: D002723:Chlorobenzoates / Q000737:chemistry; D003524:Cyclosporins / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry; D006868:Hydrolysis; D007166:Immunosuppressive Agents / Q000737:chemistry*; D007202:Indicators and Reagents; D008689:Methacrylates / Q000737:chemistry*; D010206:Papain / Q000737:chemistry; D011108:Polymers
chemical_list: D002723:Chlorobenzoates; D003524:Cyclosporins; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D008689:Methacrylates; D011108:Polymers; D010206:Papain; C000433:3-chloroperbenzoic acid; C032802:hydroxypropyl methacrylate