Trifluoroacetic Acid Mediated Additive-Free Late-Stage Native Peptide Cyclization to Form Disulfide Mimetics via Thioketalization with Ketones.
Org Lett
; 26(30): 6512-6517, 2024 Aug 02.
Article
in En
| MEDLINE
| ID: mdl-39046909
ABSTRACT
Peptide cyclization is often used to introduce conformational rigidity and to enhance the physiological stability of the peptide. This study presents a novel late-stage cyclization method for creating thioketal cyclic peptides from bis-cysteine peptides and drugs. Symmetrical cyclic ketones and acetone were found to react with bis-cysteine unprotected peptides efficiently to form thioketal linkages in trifluoroacetic acid (TFA) without any other additive. The attractive features of this method include high chemoselectivity, operational simplicity, and robustness. In addition, TFA as the reaction solvent can dissolve any unprotected peptide. As a showcase, the dimethyl thioketal versions of lanreotide and octreotide were prepared and evaluated, both of which showed much improved reductive stability and comparable activity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides, Cyclic
/
Trifluoroacetic Acid
/
Disulfides
/
Ketones
Language:
En
Journal:
Org Lett
/
Org. lett
/
Organic letters
Journal subject:
BIOQUIMICA
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos