Spadari S, Maga G, Verri A, Bendiscioli A, Tondelli L, Capobianco M, Colonna F, Garbesi A, Focher F
Istituto di Genetica Biochimica ed Evoluzionistica CNR, Pavia, Italy.
Biochimie. 1995;77(11):861-67. doi: 10.1016/0300-9084(95)90004-7.
Among enzymes involved in the synthesis of nucleotides and DNA, some exceptions have recently been found to the universal rule that enzymes act only on one enantiomer of a chiral substrate and that only one of the enantiomeric forms of chiral molecules may bind effectively at the catalytic site, displaying biological activity. The exceptions include: herpes virus thymidine kinases, cellular deoxycytidine kinase and deoxynucloside mono- and diphosphate kinases, cellular and viral DNA polymerases, such as DNA polymerase alpha, terminal transferase and HIV-1 reverse transcriptase. The ability of these enzymes to utilize unnatural L-beta-nucleosides or -nucleotides as substrate may be exploited from chemotherapeutic point of view.
在参与核苷酸和DNA合成的酶中，最近发现了一些普遍规则的例外情况。这些普遍规则是：酶仅作用于手性底物的一种对映体，并且手性分子的对映体形式中只有一种可以在催化位点有效结合并显示生物活性。这些例外包括：疱疹病毒胸苷激酶、细胞脱氧胞苷激酶以及脱氧核苷单磷酸激酶和二磷酸激酶、细胞和病毒DNA聚合酶，如DNA聚合酶α、末端转移酶和HIV-1逆转录酶。从化疗角度来看，这些酶利用非天然L-β-核苷或 - 核苷酸作为底物的能力可能会被加以利用。
