Facile synthesis of insulin fusion derivatives through sortase A ligation
| العنوان: | Facile synthesis of insulin fusion derivatives through sortase A ligation |
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| المؤلفون: | Jinze Li, Maria M. Disotuar, Nai-Pin Lin, Jake A. Smith, Danny Hung-Chieh Chou, Steve L. Alam |
| المصدر: | Acta Pharmaceutica Sinica B, Vol 11, Iss 9, Pp 2719-2725 (2021) Acta Pharmaceutica Sinica. B |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Alb, albumin, Insulin degludec, pAkt, phosphorylated protein kinase B, Boc, tert-butyloxycarbonyl, medicine.medical_treatment, Lysine, DMSO, dimethyl sulfoxide, EDT, 1,2-ethanedithiol, 0302 clinical medicine, Diabetes mellitus, HATU, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate, NBD-X, 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoic acid, t-Bu, tert-butyl, General Pharmacology, Toxicology and Pharmaceutics, HTRF, homogeneous time resolved fluorescence, Mtt, 4-methyltrityl, Insulin detemir, Long-acting insulin, 0303 health sciences, Chemistry, Albumin-binding peptide SA21, i.p., intraperitoneal, Therapeutic Insulin, DCM, dichloromethane, Biochemistry, HPLC, high performance liquid chromatography, 030220 oncology & carcinogenesis, Sortase A, DMF, dimethylformamide, Fmoc, 9-fluorenylmethoxycarbonyl, medicine.drug, DOI, desoctapeptide (B23−30) insulin, Short Communication, RM1-950, DMEM, Dulbecco's Modified Eagle Medium, STZ, streptozotocin, TIS, triisoproylsilane, 03 medical and health sciences, FBS, fetal bovine serum, Insulin synthesis, medicine, ITT, insulin tolerance test, 030304 developmental biology, Insulin, THF, triflouroacetic acid, HBTU, O-(benxontriazol-1-yl)-1,1,3,3-tetramethyluronium, Sortase A (SrtA) ligation, medicine.disease, IR-B, human insulin receptor isoform B, LC‒MS, liquid chromatography mass spectrometry, DIEA, N,N-diisopropylethylamine, Therapeutics. Pharmacology, Ligation, SrtA, sortase A |
| الوصف: | Insulin derivatives such as insulin detemir and insulin degludec are U.S. Food and Drug Administration (FDA)-approved long-acting insulin currently used by millions of people with diabetes. These derivatives are modified in C-terminal B29 lysine to retain insulin bioactivity. New and efficient methods for facile synthesis of insulin derivatives may lead to new discovery of therapeutic insulin. Herein, we report a new method using sortase A (SrtA)-mediated ligation for the synthesis of insulin derivatives with high efficiency and functional group tolerance in the C-terminal B chain. This new insulin molecule (Ins-SA) with an SrtA-recognizing motif can be conjugated to diverse groups with N-terminal oligoglycines to generate new insulin derivatives. We further demonstrated that a new insulin derivative synthesized by this SrtA-mediated ligation shows strong cellular and in vivo bioactivity. This enzymatic method can therefore be used for future insulin design and development. Graphical abstract A new method of synthesis of insulin derivatives through sortase A (SrtA) ligation was reported. The insulin substrate (Ins-SA) can be site-selectively modified using sortase A in high efficiency.Image 1 |
| اللغة: | English |
| تدمد: | 2211-3835 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a1984559319e185f56741a54626eb56Test http://www.sciencedirect.com/science/article/pii/S2211383520308017Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7a1984559319e185f56741a54626eb56 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22113835 |
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