Hydrophobic interaction of the Ca2+-calmodulin complex with calmodulin antagonists. Naphthalenesulfonamide derivatives.
Hydrophobic interaction of the Ca2+-calmodulin complex with calmodulin antagonists. Naphthalenesulfonamide derivatives.
复制标题
Ca2-钙调蛋白复合物与钙调蛋白拮抗剂的疏水相互作用。
作者：
T. Tanaka;T. Ohmura;H. Hidaka
钙调蛋白拮抗剂，如N-（6-氨基己基）-5-氯-1-萘磺酰胺（W-7），在Ca 2+存在下与钙调蛋白（CaM）结合并选择性抑制CaM诱导的酶活化，含有疏水部分。在这项研究中，没有氯分子的萘磺酰胺衍生物的疏水性比那些与氯。在Ca 2 +-CaM复合物存在下，缺氯衍生物也不太能够抑制疏水探针（2-对甲苯胺基萘-6-磺酸盐）的荧光。萘磺酰胺类化合物对Ca 2 +-CaM的亲和力与其疏水性和抑制Ca 2 +-CaM依赖性酶如Ca 2+依赖性环核苷酸磷酸二酯酶的效力密切相关。当使用具有各种长度的烷基链的衍生物时，以及当溴、氟或氰取代氯时，也观察到它们的疏水性和对Ca 2 +-CaM复合物的亲和力之间的相关性。我们的观察结果表明，这些钙调素拮抗剂可以结合的Ca ~（2+）-钙调素复合物通过疏水相互作用。
Calmodulin antagonists such as N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), which bind to calmodulin (CaM) in the presence of Ca2+ and selectively inhibit CaM-induced enzyme activation, contain a hydrophobic moiety. In this study, the naphthalenesulfonamide derivatives that lacked the chlorine molecule were less hydrophobic than those with chlorine. The chlorine-deficient derivatives also were less able to suppress the fluorescence of the hydrophobic probe (2-p-toluidinylnaphthalene-6-sulfonate) in the presence of the Ca2+-CaM complex. The affinity of naphthalenesulfonamides for Ca2+-CaM correlated well with their hydrophobicity and their potency in inhibiting Ca2+-CaM-dependent enzymes such as Ca2+-dependent cyclic nucleotide phosphodiesterase. The correlation between their hydrophobicity and affinity for the Ca2+-CaM complex also was observed when derivatives with various lengths of alkyl chain were used and when bromine, fluorine, or cyanogen was substituted for chlorine. Our observations suggest that these CaM antagonists may bind to the Ca2+-CaM complex through a hydrophobic interaction.