Peptides derived from cadherin juxtamembrane region inhibit platelet function

The juxtamembrane domains (JMD) of transmembrane proteins are rich in critical peptide sequences that participate in dynamic cell signaling events. Synthetic JMD peptides derived from cadherin cell adhesion proteins have previously been shown to modulate platelet function. In this study, we aimed to develop functional bioactive agents from bioinformatically-identified critical peptide sequences. We synthesized overlapping 12-15 amino acids peptides from E- and N-cadherin JMD and assessed their effect on platelet aggregation and platelet ATP secretion. Peptides derived from close to the membrane proximal region inhibit platelet function. Sequential deletion of amino acids from the N- and C-termini of the inhibitory E-cadherin peptides identified the short K756EPLLP763 motif as a critical bioactive sequence. Alanine scanning studies further identified that the dileucine (LL) motif and positively charged lysine (K) are crucial for peptide activity. Moreover, scrambled peptides failed to sh...

跨膜蛋白的近膜结构域（juxtamembrane domains, JMD）富含参与动态细胞信号事件的关键肽序列。此前研究表明，源自钙粘蛋白细胞粘附蛋白的合成JMD肽可调节血小板功能。本研究旨在从生物信息学鉴定的关键肽序列中开发功能性生物活性试剂。我们从E-钙粘蛋白和N-钙粘蛋白的JMD区域合成了12-15个氨基酸长度的重叠肽，并评估了它们对血小板聚集和血小板ATP分泌的影响。源自膜近端区域附近的肽可抑制血小板功能。对抑制性E-钙粘蛋白肽的N端和C端进行氨基酸连续缺失实验，确定了短序列基序K756EPLLP763为关键生物活性序列。丙氨酸扫描（Alanine scanning）研究进一步发现，双亮氨酸（LL）基序和带正电荷的赖氨酸（K）对肽活性至关重要。此外，打乱序列的肽未能发...