Fast and Stable N-Terminal Cysteine Modification through Thiazolidino Boronate Mediated Acyl Transfer.
Angew Chem Int Ed Engl
; 59(34): 14246-14250, 2020 08 17.
Article
em En
| MEDLINE
| ID: mdl-32437040
ABSTRACT
We report a novel conjugation of N-terminal cysteines (NCys) that proceeds with fast kinetics and exquisite selectivity, thereby enabling facile modification of NCys-bearing proteins in complex biological milieu. This new NCys conjugation proceeds via a thiazolidine boronate (TzB) intermediate that results from fast (k2 ≈5000 m-1 s-1 ) and reversible conjugation of NCys with 2-formylphenylboronic acid (FPBA). We designed a FPBA derivative that upon TzB formation elicits intramolecular acyl transfer to give N-acyl thiazolidines. In contrast to the quick hydrolysis of TzB, the N-acylated thiazolidines exhibit robust stability under physiologic conditions. The utility of the TzB-mediated NCys conjugation is demonstrated by rapid and non-disruptive labeling of two enzymes. Furthermore, applying this chemistry to bacteriophage allows facile chemical modification of phage libraries, which greatly expands the chemical space amenable to phage display.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácidos Borônicos
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Cisteína
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Tiazolidinas
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article