857478-11-6Relevant articles and documents
Peptidomimetics for Targeting Protein-Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL
Du, Lei,Grigsby, Sierrah M.,Yao, Aihong,Chang, Yujie,Johnson, Garrett,Sun, Haiying,Nikolovska-Coleska, Zaneta
supporting information, p. 895 - 900 (2018/09/06)
MLL-fusion proteins, AF9 and ENL, play an essential role in the recruitment of DOT1L and the H3K79 hypermethylation of MLL target genes, which is pivotal for leukemogenesis. Blocking these interactions may represent a novel therapeutic approach for MLL-rearranged leukemia. Based on the 7 mer DOT1L peptide, a class of peptidomimetics was designed. Compound 21 with modified middle residues, achieved significantly improved binding affinities to AF9 and ENL, with KD values of 15 nM and 57 nM, respectively. Importantly, 21 recognizes and binds to the cellular AF9 protein and effectively inhibits the AF9-DOT1L interactions in cells. Modifications of the N- and C-termini of 21 resulted in 28 with 2-fold improved binding affinity to AF9 and much decreased peptidic characteristics. Our study provides a proof-of-concept for development of nonpeptidic compounds to inhibit DOT1L activity by targeting its recruitment and the interactions between DOT1L and MLL-oncofusion proteins AF9 and ENL.
Ring-Opening polymerization of lactides catalyzed by natural Amino-Acid based zinc catalysts
Darensbourg, Donald J.,Karroonnirun, Osit
experimental part, p. 2360 - 2371 (2010/05/14)
A series of chiral NNO-tridentate Schiff base ligands derived from natural amino acids were reacted with zinc(bis-trimethylsilylamide)2 to provide metal complexes which have been fully characterized. One of these derivatives was further reacted
COMPOUNDS AND METHODS FOR INHIBITING THE INTERACTION OF BCL PROTEINS WITH BINDING PARTNERS
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Page/Page column 107, (2008/06/13)
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