Host-Guest Complexation by ß-Cyclodextrin Enhances the Solubility of an Esterified Protein.
Mol Pharm
; 19(11): 3869-3876, 2022 11 07.
Article
em En
| MEDLINE
| ID: mdl-36036888
ABSTRACT
The carboxyl groups of a protein can be esterified by reaction with a diazo compound, 2-diazo-2-(p-methylphenyl)-N,N-dimethylacetamide. This esterification enables the entry of the protein into the cytosol of a mammalian cell, where the nascent ester groups are hydrolyzed by endogenous esterases. The low aqueous solubility of the ensuing esterified protein is, however, a major practical challenge. Solubility screening revealed that ß-cyclodextrin (ß-CD) is an optimal solubilizing agent for esterified green fluorescent protein (est-GFP). Its addition can increase the recovery of est-GFP by 10-fold. α-CD, γ-CD, and cucurbit-7-uril are less effective excipients. 1H NMR titration experiments revealed that ß-CD encapsulates the hydrophobic tolyl group of ester conjugates with Ka = 321 M-1. Combining l-arginine and sucrose with ß-CD enables the nearly quantitative recovery of est-GFP. Thus, the insolubility of esterified proteins can be overcome with excipients.
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Base de dados:
MEDLINE
Assunto principal:
Ciclodextrinas
/
Beta-Ciclodextrinas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article