Tanaka T, Ohmura T, Hidaka H
Mol Pharmacol. 1982 Sep;22(2):403-7.
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.
钙调蛋白拮抗剂，如N-(6-氨基己基)-5-氯-1-萘磺酰胺（W-7），在Ca2+存在下与钙调蛋白（CaM）结合并选择性抑制CaM诱导的酶激活，它们含有一个疏水部分。在本研究中，缺乏氯分子的萘磺酰胺衍生物比含氯的衍生物疏水性更低。在Ca2+-CaM复合物存在的情况下，缺氯衍生物抑制疏水探针（2-对甲苯胺基萘-6-磺酸盐）荧光的能力也更低。萘磺酰胺对Ca2+-CaM的亲和力与其疏水性以及它们抑制Ca2+-CaM依赖性酶（如Ca2+依赖性环核苷酸磷酸二酯酶）的效力密切相关。当使用不同长度烷基链的衍生物以及用溴、氟或氰基取代氯时，也观察到了它们的疏水性与对Ca2+-CaM复合物亲和力之间的相关性。我们的观察结果表明，这些CaM拮抗剂可能通过疏水相互作用与Ca2+-CaM复合物结合。
