53363-79-4Relevant academic research and scientific papers
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
, p. 895 - 900 (2018)
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.
Structure of N-(tert-Butoxycarbonyl)-L-prolyl-L-valylglycine Hemihydrate
Tanaka, Isao,Ashida, Tamaichi
, p. 2164 - 2167 (1980)
C17H29N3O6*1/2H2O, Mr = 380.44, P21, a = 15.783(2), b = 13.428(2), c = 9.815(2) Angstroem, β = 90.94(1) deg, Do = 1.19, Dc (Z = 4) = 1.21 Mg m-3, m.p. 444-445 K; there are two independent molecules in
Bitter Taste of Synthetic C-Terminal Tetrapeptide of Bovine β-Casein, H-Pro196-Val-Leu-Gly-Pro-Arg-Gly-Pro-Phe-Pro-Ile-Ile-Val209-OH, and Its Related Peptides
Shinoda, Ichizo,Fushimi, Akira,Kato, Hironobu,Okai, Hideo,Fukui, Sazuko
, p. 2587 - 2596 (2007/10/02)
The primary structure of bovine β-casein contains the partial sequence of -Pro196-Val-Leu-Gly-Pro-Val-Arg-Gly-Pro-Phe-Pro-Ile-Ile-Val209 in the C-terminal portion.We previously reported that the synthetic C-terminal octapeptide, Arg202-Val209, is extremly bitter with its threshold value 0.004 mM, 250 times as strong as that of caffeine.To further investigate the bitter taste of the C-terminal portion of β-casein, we synthesized the C-terminal tetrapeptide, Pro196-Val209, and some its fragments.A hydrophobic hexapeptide, Pro196-Val201, was twice as bitter as caffein.The bitter taste of decapeptide, Pro200-Val209, was the same as that of Arg202-Val209.Although the tetradecapeptide, Pro196-Val209, was composed of two bitter peptides, Pro196-Val201 and Arg202-Val209, its bitter taste was weaker than that of Arg202-Val209 and its threshold value was 0.015 mM.We suggested that the increase of bitterness in peptides through the introduction of hydrophobic amino acids depended on the number of hydrophobic amino acids added.In addition, the synthetic retro analog of Arg202-Val209 (H-Val-Ile-Ile-Pro-Phe-Pro-Gly-Arg-OH) was not as bitter as Arg202-Val209.This indicated that the sequence of Arg202-Val209 is important for extreme bitterness.
