Citation: Hacer Karatas, Shirley Y. Lee, Elizabeth C. Townsend, Fang Cao, Jing Xu, Denzil Bernard, Liu Liu, Yali Dou, Shaomeng Wang. Structure-based design of conformationally constrained cyclic peptidomimetics to target the MLL1-WDR5 protein-protein interaction as inhibitors of the MLL1 methyltransferase activity[J]. Chinese Chemical Letters, ;2015, 26(4): 455-458. doi: 10.1016/j.cclet.2015.03.030 shu

Structure-based design of conformationally constrained cyclic peptidomimetics to target the MLL1-WDR5 protein-protein interaction as inhibitors of the MLL1 methyltransferase activity

Hacer Karatas ^a,b,c ,
Shirley Y. Lee ^d ,
Elizabeth C. Townsend ^d ,
Fang Cao ^d ,
Jing Xu ^d ,
Denzil Bernard ^b,c ,
Liu Liu ^b,c ,
Yali Dou ^d ,
Shaomeng Wang ^a,b,c,e,,

1.
a Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA;
2.
b Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA;
3.
c Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA;
4.
d Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA;
5.
e Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA

Corresponding author: Shaomeng Wang,
Received Date: 23 January 2015
Available Online: 3 March 2015
Fund Project:

We described herein structure-based design, synthesis and evaluation of conformationally constrained, cyclic peptidomimetics to block the MLL1-WDR5 protein-protein interaction as inhibitors of the MLL1 histone methyltransferase activity. Our study has yielded cyclic peptidomimetics with very high binding affinities to WDR5 (K_i values <1 nmol/L) and function as antagonists of the MLL1 histone methyltransferase activity.
- Epigenetics,
- MLL1 histone methyltransferase,
- WDR5-MLL1 interaction,
- Small-molecule inhibitors,
- Cyclic peptidomemtics
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沈阳化工大学材料科学与工程学院沈阳 110142