An in-tether chiral center modulates the proapoptotic activity of the KLA peptide

作者：Li, Jingxu; Hu, Kuan; Chen, Hailing; Wu, Yujie; Chen, Longjian; Yin, Feng^*; Tian, Yuan^*; Li, Zigang^*

来源：Chemical communications, 2017, 53(75): 10452-10455.

DOI：10.1039/c7cc04923d

• HELICAL PEPTIDES
• PERMEABILITY
• SUBSTITUTION
• STABILITY
• LYSINE

The helical peptide KLA (KLAKLAKKLAKLAK) is a well-known inducer of cellular apoptosis, acting to disrupt the mitochondrial membrane. However, its weak cellular uptake impedes development of any further applications. Here, we have utilized a novel in-tether chiral center induced helicity strategy (CIH) to develop a potent apoptosis inducer based on this KLA sequence. Notably, for the two resulting epimers of the CIH-KLA peptide, the CIH-KLA-(R) epimer exhibited superior cellular uptakes and special mitochondrial targeting when compared with its S counterpart. This work provides a promising and versatile method to modify the KLA peptide and a proof-of-concept application for the CIH strategy in modifying bioactive peptides.

• 出版日期2017-9-25
• 单位北京大学深圳研究生院; 南方医科大学; 西南交通大学