Yasuyoshi Miyachi

Enzymatic hydrolysis of random copolypeptides consisting of N-hydroxyethyl-L-glutamine and L-alanine, L-leucine, or L-valine

Abstract Two component water soluble random copolypeptides consisting of N-hydroxyethyl- l -glutamine and hydrophobic l -amino acid, such as l -alanine, l -leucine, or l -valine, were prepared by carrying out aminolysis reactions with 2-amino- l -ethanol (E) on starting copolymers consisting of γ-benzyl- l -glutamate (B) and the corresponding hydrophobic l -amino acid. The effects on copolymer composition and sequential distributions, as well as molecular conformations, on the rate of degradation by ficin in a pseudoextracellular fluid (PECF) at pH 7.4 and 37.0°C were investigated to simulate in vivo polymer degradation. All the samples were found to be extensively degraded by random chain fracture with ficin. Further, the degradation data for these samples followed the Michaelis–Menten rate law, being of the first order in ficin concentration. The nature of the side chains and the molecular conformations are important to the rate of degradation by ficin in vitro.

Biodegradation of copoly (N-hydroxyethyl-D, L-glutamine) in vitro

Abstract Random copolypeptides (PHPDLG) consisting of N-hydroxypropyl- d -glutamine (HPDG) and N-hydroxypropyl- l -glutamine (HPLG) covering the whole range of d,l -copolymer composition were prepared by carrying out aminolysis reactions with 3-amino-1-propanol (P) on starting random copolymers consisting of γ-benzyl- d -glutamate and γ-benzyl- l -glutamate (PBDLG). The effects of copolymer composition and sequential distributions on the rate of hydrolysis by papain in a pseudo-extracellular fluid (PECF) at pH 7.4 and 37.0°C were studied to simulate in vivo polymer degradation. Degradation data for these samples followed the Michaelis-Menten rate law, being of the first order to the enzyme concentration. It was shown that the rate of degradation by papain was controlled by the comonomer composition as well as sequential distributions of comonomers in the copolymer chains.

Enzymatic hydrolysis of copoly(N-hydroxypropyl-L-glutamine/L-leucine) hydrogels in vitro.

Two component random copolypeptide hydrogels consisting of N-hydroxyalkyl L-glutamine and L-leucine were prepared by carrying out aminolysis reactions with 3-amino-1-propanol(P) together with cross-linking reactors with 1,8-octamethylenediamine (OMDA) on hydrogels of the starting copolymers consisting of gamma-methyl-L-glutamate(M) and L-leucine(L). The relation between their bulk structure and properties was investigated with regard to the swelling ration in water, aqueous vapor permeability, tensile properties, and enzymatic degradation behavior in a pseudoextracellular fluid (PECF). The tensile property of the hydrogels was highly dependent on the swelling ratio in PECF, and on the hydrophobicity of the side chains, whose behavior was typical of an elastomer. It was shown that a common relation was obtained between the rate of water vapor permeabilities and the swelling ratio of hydrogels in PECF regardless of the difference of the nature of side chains. Biodegradation of the hydrogels in vitro by bromelain indicated that the degradation took place in bulk rather than on surface, and that the rate of degradation was also highly dependent on the swelling ratio of samples as well as on the hydrophobicity of the side chains of samples.