Synthesis of boronic acid derivatives of tyropeptin: proteasome inhibitors.
Boronic acid derivatives of tyropeptin were synthesized with TP-110 as the lead compound. Due to the lability of the aminoboronic acid moiety, careful design of the deprotection and coupling sequence was required. Liquid-liquid partition chromatography was found to be a powerful tool for purification of compounds of this class. The obtained derivatives showed potent inhibitory activities against the human 20S proteasome in vitro.
Watanabe
Takumi
T
Molecular Structure Research Group, Microbial Chemistry Research Center, Tokyo, Japan. twatanabe@bikaken.or.jp
Momose
Isao
I
Abe
Masatoshi
M
Abe
Hikaru
H
Sawa
Ryuichi
R
Umezawa
Yoji
Y
Ikeda
Daishiro
D
Takahashi
Yoshikazu
Y
Akamatsu
Yuzuru
Y
D001897:Boronic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors
C506903:1-naphthylacetyl-(O-methyl)-tyrosyl-valyl-(O-methyl)-tyrosinal; D001897:Boronic Acids; D004151:Dipeptides; D009842:Oligopeptides; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; C449021:tyropeptin A; C449020:tyropeptin B; D046988:Proteasome Endopeptidase Complex