Suzuki H, Ito M, Kimura T, Iwamori Y, Iwamori M
Department of Biochemistry, Faculty of Science and Technology, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Glycoconj J. 2000 Nov;17(11):787-93. doi: 10.1023/a:1010988709764.
Amphipathic sulpholipids have been shown to inhibit pancreatic serine proteases due to their detergent-like properties. To evaluate the structural requirement for this inhibitory activity, we examined the effects of various derivatives of sulphoglycolipids, some of which were prepared by deacylation with sphingolipid ceramide N-deacylase, followed by acylation with acyl chloride, on the activity of pancreatic trypsin. Both deacylated sulphatides and seminolipids exhibited inhibitory activity towards trypsin without any requirement for solubilisation and preincubation. On the other hand, stronger inhibition was observed for acylated sulphatides than for deacylated ones, but increasing the chain length of the fatty acid moiety resulted in the need for a solubilisation agent and preincubation in order to achieve maximal inhibitory activity. The structural isomers of sulphoglycolipids, such as I(6)SO(3)-GalCer, and phytosphingosine- and diglyceride-containing sulphoglycolipids, showed similar inhibitory activity, indicating the involvement of sulphate and hydrophobic groups, irrespective of the fine structure, in the inhibition. Among the sulphoglycolipids examined, II(3)SO(3)-LacCer was found to exhibit the highest inhibitory activity.
两亲性硫脂因其类似去污剂的性质已被证明可抑制胰腺丝氨酸蛋白酶。为了评估这种抑制活性的结构要求，我们研究了硫糖脂的各种衍生物对胰蛋白酶活性的影响，其中一些衍生物是通过用鞘脂神经酰胺N - 脱酰酶进行脱酰作用，然后用酰氯进行酰化制备的。脱酰化的硫苷脂和半乳糖脑苷脂硫酸酯对胰蛋白酶均表现出抑制活性，且无需溶解和预孵育。另一方面，观察到酰化硫苷脂的抑制作用比脱酰化的更强，但增加脂肪酸部分的链长导致需要增溶剂和预孵育才能达到最大抑制活性。硫糖脂的结构异构体，如I(6)SO(3)-半乳糖神经酰胺，以及含植物鞘氨醇和甘油二酯的硫糖脂，表现出类似的抑制活性，表明无论精细结构如何，硫酸盐和疏水基团均参与了抑制作用。在所研究的硫糖脂中，II(3)SO(3)-乳糖神经酰胺被发现具有最高的抑制活性。
