- Expanding the Structural Diversity of Protein Building Blocks with Noncanonical Amino Acids Biosynthesized from Aromatic Thiols
-
Incorporation of structurally novel noncanonical amino acids (ncAAs) into proteins is valuable for both scientific and biomedical applications. To expand the structural diversity of available ncAAs and to reduce the burden of chemically synthesizing them, we have developed a general and simple biosynthetic method for genetically encoding novel ncAAs into recombinant proteins by feeding cells with economical commercially available or synthetically accessible aromatic thiols. We demonstrate that nearly 50 ncAAs with a diverse array of structures can be biosynthesized from these simple small-molecule precursors by hijacking the cysteine biosynthetic enzymes, and the resulting ncAAs can subsequently be incorporated into proteins via an expanded genetic code. Moreover, we demonstrate that bioorthogonal reactive groups such as aromatic azides and aromatic ketones can be incorporated into green fluorescent protein or a therapeutic antibody with high yields, allowing for subsequent chemical conjugation.
- Wang, Yong,Chen, Xiaoxu,Cai, Wenkang,Tan, Linzhi,Yu, Yutong,Han, Boyang,Li, Yuxuan,Xie, Yuanzhe,Su, Yeyu,Luo, Xiaozhou,Liu, Tao
-
supporting information
p. 10040 - 10048
(2021/03/26)
-
- Unnatural amino acid synthesis by thermostable O-phospho-L-serine sulfhydrylase from hyperthermophilic archaeon Aeropyrum pernix K1
-
O-Acetyl-L-serine sulfhydrylase (OASS) from plants and bacteria synthesizes cysteine and unnatural amino acids that are important building blocks for active pharmaceuticals and agrochemicals. A thermostable O-phospho-L-serine sulfhydrylase from hyperthermophilic archaeon Aeropyrum pernix K1 (OPSSAp) exhibits a function similar to OASS. In the present study, we examined the synthesis of various unnatural amino acids using OPSSAp and demonstrated OPSSAp could efficiently synthesize various sulfur-containing amino acids. OPSSAp would be useful for industrial production of biologically important unnatural amino acids.
- Nakamura, Takashi,Kunimoto, Kohei,Yuki, Toru,Ishikawa, Kazuhiko
-
supporting information
p. 1789 - 1792
(2017/11/23)
-
- Synthesis and Antitumor activity of Cysteinyl-3,4-dihydroxyphenylalanines and Related Compounds
-
The natural catecholic amino acid 5-S-cysteinyl-3,4-dihydroxyphenylalanine (1) was selectively toxic to a variety of human tumor cell lines in culture and exhibited antitumor activity against L1210 leukemia and B-16 melanoma in mice at doses which were not toxic to the host.Structural analogues of 5-S-cysteinyl-3,4-dihydroxyphenylalanine, including several new compounds, were synthesized and tested for growth inhibition of cultured cells of human neuroblastoma YT-nu and Chinese hamster fibroblast Don-6.Some were also examined for antitumor activity against L1210 and B-16 in vivo. 4-S-Cysteinylcatechols and 2- and 4-S-cysteinylphenols, which cannot be prepared by conventional methods, were synthesized by the reaction of catechols and phenols with cystine in boiling aqueous HBr. 5-S-Cysteinyl and 2-S-cysteinyl-3,4-dihydroxyphenylalanine (1 and 2), L-3,4-dihydroxyphenylalanine (L-Dopa), and 2- and 4-S-cysteinylphenol (14 and 15) were toxic to the YT-nu cell line only, while 4-S-cysteinylcatechol (6), 3-S-cysteinyl-5-methylcatechol (8), 5-S-cysteaminyldopamine (9), and 4-methylcatechol were strongly toxic to both cell lines.Compounds 1 (1000 mg/kg), 6 (500 mg/kg), and 8 (400 mg/kg) increased the life span of L1210-bearing mice by 50, 50, and 43percent, respectively, and compounds 1 and 8 were marginally effective against B-16 melanoma as well.Compound 9 was too toxic to show any activity.There was good correlation between the cytotoxicity and the in vivo activity.
- Ito, Shosuke,Inoue, Shigeki,Yamamoto, Yoshinobu,Fujita, Keisuke
-
p. 673 - 677
(2007/10/02)
-
- STUDIES ON PEPTIDES. XCVI. BEHAVIOR OF S-ACETAMIDOMETHYLCYSTEINE SULFOXIDE UNDER DEPROTECTING CONDITIONS IN PEPTIDE SYNTHESIS
-
The sulfoxide of Boc-Cys(S-acetamidomethyl)-OH was prepared by oxidation with sodium perborate.Mercuric acetate and iodine failed to cleave the S-protecting group from sulfoxide.Hydrogen fluoride and methanesulfonic acid partially converted the sulfoxide to S-p-methoxyphenylcysteine in the presence of anisole.A reducing reagent, thiophenol, converted the sulfoxide to acetamidomethyl phenyl sulfide and Nα-Boc-S-(phenylthio)cysteine.Keywords - S-acetamidomethylcysteine sulfoxide; mercuric acetate treatment; iodine treatment; hydrogen fluoride treatment; methanesulfonic acid treatment; thiophenol treatment
- Yajima, Haruaki,Akaji, Kenichi,Funakoshi, Susumu,Fujii, Nobutaka,Irie, Hiroshi
-
p. 1942 - 1945
(2007/10/02)
-