Stabilization of a Protein by a Single Halogen-Based Aromatic Amplifier

Autor: Krystel El Hage, Nelson B. Phillips, Yen-Shan Chen, Balamurugan Dhayalan, Jonathan Whittaker, Kelley Carr, Linda Whittaker, Manijeh H. Phillips, Faramarz Ismail-Beigi, Markus Meuwly, Michael A. Weiss

The utility of halogenation in protein design is investigated by a combination of quantitative atomistic simulations and experiment. The approach is applied to insulin, a small, therapeutically relevant domain amenable to simulation and semi-synthesi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::e7b5e6bc8c26a2edb3296decfd2c8a1d
https://doi.org/10.1101/2022.07.25.501420

Contribution of TyrB26 to the Function and Stability of Insulin

Autor: Michael C. Lawrence, Nischay K. Rege, Jonathan Whittaker, Vijay Pandyarajan, Nelson B. Phillips, Michael A. Weiss

Publikováno v: Journal of Biological Chemistry. 291:12978-12990

Crystallographic studies of insulin bound to receptor domains have defined the primary hormone-receptor interface. We investigated the role of TyrB26, a conserved aromatic residue at this interface. To probe the evolutionary basis for such conservati

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::9f5acbe13b74dfb509cc3ff0caf2512a
https://doi.org/10.1074/jbc.m115.708347

An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein

Autor: Michael C. Lawrence, Manijeh Phillips, Nalinda P. Wickramasinghe, Faramarz Ismail-Beigi, Nelson B. Phillips, Jonathan Whittaker, Kelley Carr, Michael D. Glidden, Yanwu Yang, Khadijah Aldabbagh, Nischay Rege, Yen Shan Chen, Michael A. Weiss, Mamuni Swain, Yi Peng, Vivien C. Yee

Thermal degradation of insulin complicates its delivery and use. Previous efforts to engineer ultra-stable analogs were confounded by prolonged cellular signaling in vivo, of unclear safety and complicating mealtime therapy. We therefore sought an ul

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f08dc8ce4ba088ce3c8e664fec15372
https://europepmc.org/articles/PMC5766902/

Biophysical Optimization of a Therapeutic Protein by Nonstandard Mutagenesis

Autor: Yanwu Yang, Nelson B. Phillips, Faramarz Ismail-Beigi, Vijay Pandyarajan, Michael A. Weiss, Gabriela P. Cox, Jonathan Whittaker

Publikováno v: Journal of Biological Chemistry. 289:23367-23381

Insulin provides a model for the therapeutic application of protein engineering. A paradigm in molecular pharmacology was defined by design of rapid-acting insulin analogs for the prandial control of glycemia. Such analogs, a cornerstone of current d

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::bc2f16ecfdea531edbea93caaf03252d
https://doi.org/10.1074/jbc.m114.588277

Extending Halogen-based Medicinal Chemistry to Proteins: IODO-INSULIN AS A CASE STUDY

Autor: Krystel El Hage, Nelson B. Phillips, Brian J. Smith, Michael A. Weiss, Vijay Pandyarajan, Markus Meuwly, Michael C. Lawrence, John G. Menting, Jonathan Whittaker

Publikováno v: Journal of Biological Chemistry
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2016, 291 (53), pp.27023-27041. ⟨10.1074/jbc.M116.761015⟩

International audience; Insulin, a protein critical for metabolic homeostasis, provides a classical model for protein design with application to human health. Recent efforts to improve its pharmaceutical formulation demonstrated that iodination of a

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b13c26c8774515dd40e5a5d24618f3bc
https://hal-univ-evry.archives-ouvertes.fr/hal-02160383