التفاصيل البيبلوغرافية
| العنوان: |
Molecular Engineering of Efficacious Mono-Valent Ultra-Long Acting Two-Chain Insulin-Fc Conjugates |
| المؤلفون: |
Tina M. Tagmose (2715901), Karen-Margrethe Pedersen (12029890), Lone Pridal (2375119), Carsten E. Stidsen (9193879), Marie Ø. Pedersen (2245372), Zhaosheng Lin (12029893), Yuanyuan Zhang (101797), Zhe Wan (74018), Mercedes Ferreras (12029896), Helle Naver (10745027), Peter K. Nielsen (2684311), Zheng Cao (562710), Yi Wang (32470), Lennart Lykke (1766620), Josefine L. Christensen (12029899), Victoria S. Jensen (12029902), Valentina Manfè (9920942), Thomas Å. Pedersen (12029905), Eva Johansson (335751), Peter Madsen (2242984), János T. Kodra (2375125), Martin Münzel (1485277), Leonardo De Maria (416956), Erica Nishimura (197646), Thomas B. Kjeldsen (10745024) |
| سنة النشر: |
2022 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biophysics, Biochemistry, Genetics, Molecular Biology, Physiology, Pharmacology, Biotechnology, Immunology, Cancer, Virology, Computational Biology, Chemical Sciences not elsewhere classified, disulfide bond within, amino acid substitutions, long acting two, neonatal fc receptor, fc conjugation leads, long pharmacokinetic profile, insulin receptor affinity, describe molecular engineering, long pharmacokinetic, molecular engineering, fc molecule, fc element, fc conjugates, molecular size, pharmacodynamic profiles, mediated clearance, lysine residue, efficacious mono |
| الوصف: |
Here, we describe molecular engineering of monovalent ultra-long acting two-chain insulin-Fc conjugates. Insulin-Fc conjugates were synthesized using trifunctional linkers with one amino reactive group for reaction with a lysine residue of insulin and two thiol reactive groups used for re-bridging of a disulfide bond within the Fc molecule. The ultra-long pharmacokinetic profile of the insulin-Fc conjugates was the result of concertedly slowing insulin receptor-mediated clearance by (1) introduction of amino acid substitutions that lowered the insulin receptor affinity and (2) conjugating insulin to the Fc element. Fc conjugation leads to recycling by the neonatal Fc receptor and increase in the molecular size, both contributing to the ultra-long pharmacokinetic and pharmacodynamic profiles. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/Molecular_Engineering_of_Efficacious_Mono-Valent_Ultra-Long_Acting_Two-Chain_Insulin-Fc_Conjugates/19104754Test |
| DOI: |
10.1021/acs.jmedchem.1c02039.s001 |
| الإتاحة: |
https://doi.org/10.1021/acs.jmedchem.1c02039.s001Test |
| حقوق: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.2E3A5BE |
| قاعدة البيانات: |
BASE |
