Pursuit of a perfect insulin

AN Zaykov, JP Mayer, RD DiMarchi - Nature Reviews Drug Discovery, 2016 - nature.com
Insulin remains indispensable in the treatment of diabetes, but its use is hampered by its
narrow therapeutic index. Although advances in peptide chemistry and recombinant DNA …

[HTML][HTML] 'Smart'insulin-delivery technologies and intrinsic glucose-responsive insulin analogues

MA Jarosinski, B Dhayalan, N Rege, D Chatterjee… - Diabetologia, 2021 - Springer
Insulin replacement therapy for diabetes mellitus seeks to minimise excursions in blood
glucose concentration above or below the therapeutic range (hyper-or hypoglycaemia). To …

Synergistic activation of the insulin receptor via two distinct sites

J Li, J Park, JP Mayer, KJ Webb, E Uchikawa… - Nature structural & …, 2022 - nature.com
Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four
insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise …

Glucose-responsive insulin by molecular and physical design

NA Bakh, AB Cortinas, MA Weiss, RS Langer… - Nature …, 2017 - nature.com
The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes
technology. The idea behind the GRI is to create a therapeutic that modulates its potency …

The chemical synthesis of insulin: an enduring challenge

JA Karas, JD Wade, MA Hossain - Chemical reviews, 2021 - ACS Publications
The pancreatic peptide hormone insulin, first discovered exactly 100 years ago, is essential
for glycemic control and is used as a therapeutic for the treatment of type 1 and, increasingly …

Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling: A paradigm shift for host–microbe interactions

E Altindis, W Cai, M Sakaguchi… - Proceedings of the …, 2018 - National Acad Sciences
Viruses are the most abundant biological entities and carry a wide variety of genetic
material, including the ability to encode host-like proteins. Here we show that viruses carry …

Insertion of a synthetic switch into insulin provides metabolite-dependent regulation of hormone–receptor activation

YS Chen, J Gleaton, Y Yang… - Proceedings of the …, 2021 - National Acad Sciences
Insulin-signaling requires conformational change: whereas the free hormone and its
receptor each adopt autoinhibited conformations, their binding leads to structural …

Substitution of an internal disulfide bridge with a diselenide enhances both foldability and stability of human insulin

O Weil‐Ktorza, N Rege, S Lansky… - … A European Journal, 2019 - Wiley Online Library
Insulin analogues, mainstays in the modern treatment of diabetes mellitus, exemplify the
utility of protein engineering in molecular pharmacology. Whereas chemical syntheses of the …

The ABC of insulin: the organic chemistry of a small protein

M Østergaard, NK Mishra… - Chemistry–A European …, 2020 - Wiley Online Library
Insulin is a small protein crucial for regulating the blood glucose level in all animals. Since
1922 it has been used for the treatment of patients with diabetes. Despite consisting of just …

Insulin—from its discovery to the industrial synthesis of modern insulin analogues

L Moroder, HJ Musiol - Angewandte Chemie International …, 2017 - Wiley Online Library
After the discovery of insulin as a drug for diabetes, the pharmaceutical companies were
faced with the challenge to meet the demand for insulin with the highest possible degree of …