Biomimetic Synthesis of Insulin Enabled by Oxime Ligation and Traceless 'C-Peptide' Chemical Excision
| Autor: | Vasily M. Gelfanov, Binbin Kou, Richard D. DiMarchi, Kishore Thalluri, John P. Mayer, Fa Liu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_treatment
Ester hydrolysis 010402 general chemistry 01 natural sciences Biochemistry Redox chemistry.chemical_compound Biomimetics Biomimetic synthesis Oximes medicine Insulin Amino Acid Sequence Physical and Theoretical Chemistry C-Peptide Molecular Structure 010405 organic chemistry Chemistry C-peptide Organic Chemistry Oxime Combinatorial chemistry 0104 chemical sciences Ligation Linker |
| Zdroj: | Organic Letters. 19:706-709 |
| ISSN: | 1523-7052 1523-7060 |
| DOI: | 10.1021/acs.orglett.6b03876 |
| Popis: | For decades, insulin has represented a preeminent synthetic target. Recently introduced "biomimetic" strategies based on convertible single-chain precursors require incorporation of a chemical linker or a unique proteolytic site, which limits their practicality. In this approach the A- and B-chains are linked by two sequential oxime ligations followed by disulfide bond formation under redox conditions and linker excision by diketopiperazine (DKP) formation and ester hydrolysis, yielding native two-chain insulin. The method is expected to be applicable to any member of the insulin superfamily. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|