66315-15-9Relevant articles and documents
A chemical approach for the synthesis of the DNA-binding domain of the oncoprotein MYC
Calo-Lapido, Renata,Penas, Cristina,Jiménez-Balsa, Adrián,Vázquez, M. Eugenio,Mascare?as, José L.
, p. 6748 - 6752 (2019/07/22)
We describe the first chemical synthesis of a functional mutant of the DNA binding domain of the oncoprotein MYC, using two alternative strategies which involve either one or two Native Chemical Ligations (NCLs). Both routes allowed the efficient synthesis of a miniprotein which is capable of heterodimerizing with MAX, and replicate the DNA binding of the native protein. The versatility of the reported synthetic approach enabled the straightforward preparation of MYC and Omomyc analogues, as well as fluorescently labeled derivatives.
Synthesis of a secretoglobin 3A2 type C (98–139) fragment by Dawson's native chemical ligation
Kikuchi, Mariko,Kurotani, Reiko,Konno, Hiroyuki
, p. 4145 - 4148 (2017/09/29)
A secretoglobin 3A2 type C (98–139) peptide was synthesized by native chemical ligation between 115Ile and 116Cys residues using Dawson's linker. The peptide-N-acyl-benzimidazolinone-glycine amide, a C-terminal thioesters precursor, was provided from 3-amino-4-(methylamino)benzoic acid. In addition, an N-terminal cysteine fragment, the (116–139) peptide, was prepared by ordinary Fmoc-solid phase peptide synthesis. Native chemical ligation of the (98–115) fragment with the Dawson's linker and the (116–139) peptide smoothly proceeded to give SCGB3A2 type C (98–139) peptide.
Chemical Protein Synthesis Using a Second-Generation N-Acylurea Linker for the Preparation of Peptide-Thioester Precursors
Blanco-Canosa, Juan B.,Nardone, Brunello,Albericio, Fernando,Dawson, Philip E.
, p. 7197 - 7209 (2015/06/25)
The broad utility of native chemical ligation (NCL) in protein synthesis has fostered a search for methods that enable the efficient synthesis of C-terminal peptide-thioesters, key intermediates in NCL. We have developed an N-acylurea (Nbz) approach for the synthesis of thioester peptide precursors that efficiently undergo thiol exchange yielding thioester peptides and subsequently NCL reaction. However, the synthesis of some glycine-rich sequences revealed limitations, such as diacylated products that can not be converted into N-acylurea peptides. Here, we introduce a new N-acylurea linker bearing an o-amino(methyl)aniline (MeDbz) moiety that enables in a more robust peptide chain assembly. The generality of the approach is illustrated by the synthesis of a pentaglycine sequence under different coupling conditions including microwave heating at coupling temperatures up to 90 C, affording the unique and desired N-acyl-N′-methylacylurea (MeNbz) product. Further extension of the method allowed the synthesis of all 20 natural amino acids and their NCL reactions. The kinetic analysis of the ligations using model peptides shows the MeNbz peptide rapidly converts to arylthioesters that are efficient at NCL. Finally, we show that the new MeDbz linker can be applied to the synthesis of cysteine-rich proteins such the cyclotides Kalata B1 and MCoTI-II through a one cyclization/folding step in the ligation/folding buffer. (Chemical Equation Presented).
