Synthesis and Characterization of an A6-A11 Methylene Thioacetal Human Insulin Analogue with Enhanced Stability
Insulin has been a life-saving drug for millions of people with diabetes. However, several challenges exist which limit therapeutic benefits and reduce patient convenience. One key challenge is the fibrillation propensity, which necessitates refrigeration for storage. To address this limitation, we...
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| Veröffentlicht in: | Journal of medicinal chemistry 2019-12, Vol.62 (24), p.11437-11443 |
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| container_end_page | 11443 |
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| container_issue | 24 |
| container_start_page | 11437 |
| container_title | Journal of medicinal chemistry |
| container_volume | 62 |
| creator | Zheng, Nan Karra, Prasoona VandenBerg, Michael A Kim, Jin Hwan Webber, Matthew J Holland, William L Chou, Danny Hung-Chieh |
| description | Insulin has been a life-saving drug for millions of people with diabetes. However, several challenges exist which limit therapeutic benefits and reduce patient convenience. One key challenge is the fibrillation propensity, which necessitates refrigeration for storage. To address this limitation, we chemically synthesized and evaluated a methylene thioacetal human insulin analogue (SCS-Ins). The synthesized SCS-Ins showed enhanced serum stability and aggregation resistance while retaining bioactivity compared with native insulin. |
| doi_str_mv | 10.1021/acs.jmedchem.9b01589 |
| format | Article |
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| ispartof | Journal of medicinal chemistry, 2019-12, Vol.62 (24), p.11437-11443 |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Amino Acid Sequence Animals Disulfides - chemistry Disulfides - metabolism Drug Design Drug Stability Female Humans Insulin - chemistry Insulin - metabolism Male Mice Mice, Inbred C57BL Peptide Fragments - chemistry Peptide Fragments - metabolism Protein Conformation Sulfhydryl Compounds - chemistry |
| title | Synthesis and Characterization of an A6-A11 Methylene Thioacetal Human Insulin Analogue with Enhanced Stability |
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