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Z is independently selected from the group consisting of one or more amino acid(s), one or more N-substituted amino acid, optionally substituted polyether, C1-C12 alkylene, arylene having 6 to 10 ring atoms, C3-C8 cycloalkylene, heterocycloalkylene having 5 to 10 ring atoms, heteroarylene having 5 to 10 ring atoms, C2-C10 alkenylene, and any combination thereof, said alkylene and alkenylene being optionally interrupted by one or more heteroatom or chemical groups selected from -O-, -S-, -C(O)-, -NR-, -C(O)NR- , -NR-C(O)-, -NR-C(O)-NR-, -NR-C(O)-O-, -O-C(O)NR- and triazole, and said alkylene, arylene, cycloalkylene, heterocycl R, R and R being independently selected from H and Ci-Ce alkyl

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Therefore, the expression of ME2 and ME3 evolved to be low in astrocytes where PC expression is high, and the expression of PC evolved to be low in neurons where ME3 expression is moderate (Supplementary Table 1)

Taken together, the NMR and DFT studies show that the 1,6-addition is highly regioselective and only yields a single product