No abstract

Nonblended poly(L-lactide) (PLLA) films having different molecular weights and nonblended poly(lactide) (PLA) films, enantiomeric blend films from PLLA and poly(D-lactide) (PDLA), and diastereoisomeric blend films of poly(DL-lactide) (PDLLA) with either PLLA or PDLA, having different L-lactide (LLA) contents (X(LLA)s) in the range of 0-0.99, were amorphous made by melt-quenching. The effects of molecular weight, X(LLA), and average L- and D-lactyl unit sequence length (l(L) and l(D), respectively) on the enzymatic hydrolysis of the films were investigated in the presence of proteinase K. The enzymatic hydrolysis rate (R(EH)) of PLLA estimated by gravimetry increased monotonically with the inverse of number-average molecular weight (M(n)). The extrapolation of R(EH) of PLLA to M(n)(-1) = 0, where no exo-chain-scission takes place, gave a positive R(EH) value (1.75 microg/(mm(2).h)), meaning that the enzymatic hydrolysis of PLLA proceeds via both endo- and exo-chain-scission. The R(EH) of the nonblended films as well as the enantiomeric and diastereoisomeric blend films decreased monotonically with the decease in X(LLA) and finally became zero for X(LLA) below 0.3. The R(EH) values of the blend films of PLLA and PDLLA with PDLA (l(D) = infinity) were lower than expected, while the R(EH) values of the blend films of PLLA with PDLLA (l(D) = 4) agreed completely with the expected values. These results reveal that the nonblended PLA films are enzymatically hydrolyzable when X(LLA) and l(L) are higher than 0.3 and 3, respectively, and l(D) is lower than 10 and that the presence of long D-lactyl unit sequences (l(D) > 4) as in PDLA hinders the enzymatic hydrolysis of long L-lactyl unit sequences even when long D- and L-lactyl unit sequences are present in the different molecules.

No abstract

Cyclin-dependent kinase 5 (Cdk5) is activated by binding to its activators, p35 and p39. The level of Cdk5 activity is determined by the amount of p35 and p39, which is regulated not only by transcription but also via proteasomal degradation. Alternatively, calpain-induced cleavage of p35 to p25 can induce aberrant Cdk5 activation. As the regulation of p35 and p39 proteolysis is not well understood, we have studied here the mechanisms governing their degradation and cleavage. We find that p35 and p39 undergo proteasomal degradation in neurons, with p39 showing a slower degradation rate than p35. Degradation of the activators is dependent on their respective N-terminal p10 region, as indicated by experiments in which cognate p10 regions were swapped between p35 and p39. The effect of the p10 region on degradation and cleavage could be assigned to its membrane binding properties, mediated predominantly by myristoylation. Together, these results indicate that both proteasomal degradation and calpain cleavage of p35 and p39 are stimulated by membrane association, which is in turn mediated via myristoylation of their p10 regions. However, p35 and p39 show differences in degradation and cleavage rates, which may in fact underlie the distinct physiological and pathological functions of these two Cdk5 activators.