Synthesis and enzymatic degradation of optically active depsipeptide copolymers.
This paper describes the synthesis and biodegradation of copolymers of cyclic depsipeptide with epsilon-caprolactone (CL) or lactide (LA). Optically active cyclic depsipeptides, 3,6-dimethyl-2,5-morpholinediones (DMOs), were prepared by the reaction of an amino acid (D-, L-, or DL-alanine) with a hydroxy acid derivative (DL-2-bromopropionyl bromide). These isomers are abbreviated as D-DMO, L-DMO and DL-DMO respectively, according to the names of alanine isomers. Then, we have prepared the copolymers of DMO isomers with CL using tin(II) octylate as a catalyst. The NMR spectra and thermal properties of DMO/CL copolymers revealed that these copolymers exist randomly. The enzymatic degradation of the copolymers has been examined using Rhizopus delemar lipase, cholesterol esterase (from Pseudomonas sp.), and Proteinase K (from Tritirachium album). Cholesterol esterase and Proteinase K show high degradability, while the lipase shows little degradation. Among the enzymes used, only Proteinase K could recognize the isomerism of DMO, resulting in the following order of degradability: copoly(L-DMO/CL) > copoly(DL-DMO/CL) > copoly(D-DMO/CL), i.e. this enzyme has the highest substrate specificity for naturally occurring L-alanine. Further, we have prepared the random copolymers of L-DMO with lactide (L-LA or DL-LA), and evaluated the enzymatic degradation of the copolymers by Proteinase K. The introduction of a small amount (up to c. 10 mol%) of L-DMO unit into LA homopolymers brought about greater degradability compared with LA homopolymers. In particular, L-DMO/L-LA copolymers with high degradability have been obtained without significant decrease in the mechanical and thermal properties of L-LA homopolymer.
Shirahama
H
H
Department of Applied Chemistry, Faculty of Engineering, Hiroshima University, Higashi-Hiroshima, Japan.
Umemoto
K
K
Yasuda
H
H
D019286:Endopeptidase K / Q000378:metabolism; D007536:Isomerism; D008855:Microscopy, Electron, Scanning; D010456:Peptides, Cyclic / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis*; D013696:Temperature; D013997:Time Factors
D010456:Peptides, Cyclic; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D019286:Endopeptidase K