Total chemical synthesis of the N-terminal domain of TIMP2

Abstract

The migration and invasion of tumor cells are major contributors to mortality in malignant tumors. Studies have shown that matrix metalloproteinase 14 (MMP14) plays a crucial role in promoting tumor cell metastasis. Its activity can be suppressed by tissue inhibitor of metalloproteinases 2 (TIMP2), which acts as a natural inhibitor. However, the development of MMP14 inhibitors for clinical use has been unsuccessful, partly due to the unclear mechanism of the interaction between TIMP2 and MMP14. In this work, we successfully obtained the N-terminal domain of TIMP2 (N-TIMP2) protein through a four-segment-three-ligation total chemical synthesis strategy and confirmed its correct refolding, thus providing a novel tool for elucidating the specific interaction mechanisms between N-TIMP2 and MMP14.