title: Novel solid-phase synthesis of thiol-terminated-poly(alpha-amino acid)-drug conjugate.
abstract: A new method using a controlled pore glass solid support for the preparation of a thiol-terminated-polymerdrug, notably poly-L-glutamate-daunomycin having a terminal thiol group, is described. The method consists of first polymerizing an ester-protected glutamic acid onto an amino-disulfide functionalized controlled pore glass support. The ester protecting group is then removed, freeing the gamma-carboxyl groups of the grafted polymer which then allows it to react with daunomycin. Finally, the disulfide bond linking the conjugated polymer-drug to the solid support is broken by thiolysis, thus releasing the desired product. The final product consists of only polymer-drug conjugates with terminal thiol groups (global yield 26%). This novel method is much simpler and more elegant than more conventional preparation methods requiring solution phase techniques.
authors.affiliation: Sintetica S.A., Research Center, Carouge-Geneva, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Palacios
authors.forename: P
authors.initials: P
authors.lastname: Bussat
authors.forename: D
authors.initials: D
authors.lastname: Bichon
mesh_terms: D011232:Chemical Precipitation; D003630:Daunorubicin / Q000138:chemical synthesis*; D004339:Drug Compounding / Q000379:methods; D011099:Polyglutamic Acid / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D011108:Polymers; D013438:Sulfhydryl Compounds; D011099:Polyglutamic Acid; D003630:Daunorubicin