111524-95-9Relevant articles and documents
Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)-Mixed Lineage Leukemia (MLL) Protein-Protein Interaction
Karatas, Hacer,Li, Yangbing,Liu, Liu,Ji, Jiao,Lee, Shirley,Chen, Yong,Yang, Jiuling,Huang, Liyue,Bernard, Denzil,Xu, Jing,Townsend, Elizabeth C.,Cao, Fang,Ran, Xu,Li, Xiaoqin,Wen, Bo,Sun, Duxin,Stuckey, Jeanne A,Lei, Ming,Dou, Yali,Wang, Shaomeng
, p. 4818 - 4839 (2017)
We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5-mixed lineage leukemia (MLL) protein-protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value 50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis for their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5-MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.
Development of a rapid, room-temperature dynamic kinetic resolution for efficient asymmetric synthesis of α-aryl amino acids
Hang, Jianfeng,Li, Hongming,Deng, Li
, p. 3321 - 3324 (2007/10/03)
equation presented A rapid, highly efficient and general dynamic kinetic resolution (DKR) of racemic α-aryl UNCAs with the dual-function catalysis of modified cinchona alkaloid was accomplished at room temperature. This DKR led to the development of a highly enantioselective catalytic method for the practical synthesis of a wide range of α-aryl and α-heteroaryl amino acids in 89-92% ee and 86-95% yield from racemic UNCAs.
SIMULTANEOUS USE OF N-Fmoc AND OTmse PROTECTIVE GROUPS IN THE SYNTHESIS OF PEPTOLYTIC SENSITIVE PEPTIDES
Vanfleteren, L.,Anteunis, M. J. O.
, p. 505 - 518 (2007/10/02)
The combined use of Fmoc (fluorenylmethoxycarbonyl) as N-protection and Tmse (trimethylsilylethyl) as O-protection during demanding fragment condensation mediated by Bop-Cl (N,N'-bis(3-oxo-2-oxazolidinyl)phosphinyl chloride) has been explored in the preparation of useful synthons that are sensitive to acidic and even basic hydrolyses.Stepwise deprotection by morfoline (Fmoc-deprotection) followed by F--mediated removal of Tmse results in a very effective peptide synthesis strategy, as exemplified by the preparation of i.a.Phg-MePhe-Thz.Similarly, combinations of N-Boc, O-Tmse peptide esters are also possible that allow the preparation of +H2-MePhe-Thz-OTmse (via Boc-MePhe-Thz-OTmse) without competitive DKP formation.
