Growth‐receptor bound 7 (Grb7) is an adapter protein identified as a target for the inhibition of signaling pathways in breast and other cancers. We have previously developed cyclic and bicyclic G7‐peptide inhibitors, targeted to the Grb7‐SH2 domain, and used the cell‐penetrating peptide (CPP) penetratin to deliver them to cells to test their biological effects. Here we used an alternative peptide known as cyclic TAT (cTAT) to determine whether it would be more effective for the delivery of the G7‐peptides. We report the synthesis of propargyl‐cTAT for the conjugation to azido‐peptides G7‐18NATE and G7‐B7M2 via click chemistry. We then compare these peptides with G7‐18NATE‐Pen and G7‐B7M2‐Pen for their ability to inhibit signaling, proliferation, migration and, invasion of SKBR‐3 and MDA‐MB‐231 breast cancer cell lines. We found both penetratin and cTAT conjugated G7‐peptides were able to enter cells and exert biological effects but that cTAT was not more effective than penetratin for delivery of G7‐18NATE, and neither CPP was highly effective for the delivery of G7‐B7M2 in cell assays.

中文翻译：

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可点击的环状TAT和渗透肽在递送环状和双环肽货物中的比较

生长受体结合7（Grb7）是一种衔接蛋白，被确定为抑制乳腺癌和其他癌症信号通路的靶标。我们之前已经开发了针对Grb7-SH2结构域的环状和双环G7肽抑制剂，并使用细胞穿透肽（CPP）渗透素将其递送至细胞以测试其生物学效应。在这里，我们使用了一种称为环TAT（cTAT）的替代肽来确定它是否对递送G7肽更有效。我们通过点击化学报道了炔丙基-cTAT与叠氮基肽G7-18NATE和G7-B7M2共轭的合成方法。然后，我们将这些肽与G7-18NATE-Pen和G7-B7M2-Pen的抑制信号传导，增殖，迁移和侵袭SKBR-3和MDA-MB-231乳腺癌细胞系的能力进行比较。