ArticleScientific reports2017
Insulin in motion: The A6-A11 disulfide bond allosterically modulates structural transitions required for insulin activity.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Systematic analysis of loss-of-function variants across MODY genes demonstrates gene-specific effects and expands the spectrum of INS variants causing MODY.Diabetologia · 2026Article
- Sulfur-Dependent Disulfide Bond Disruption in Insulin Resistance: A Hypothesis.Advanced pharmaceutical bulletin · 2025Article
- Seleno-relaxin analogues: effect of internal and external diselenide bonds on the foldability and a fibrosis-related factor of endometriotic stromal cells.RSC chemical biology · 2024Article
- Raman Spectroscopic Insights of Phase-Separated Insulin Aggregates.ACS physical chemistry Au · 2024Article
- Semisynthesis of A6-A11 lactam insulin.Journal of peptide science : an official publication of the European Peptide Society · 2024Article
- An Investigation into the Acidity-Induced Insulin Agglomeration: Implications for Drug Delivery and Translation.ACS omega · 2023Article
- Synthesis of Cystine-Stabilised Dicarba Conotoxin EpI: Ring-Closing Metathesis of Sidechain Deprotected, Sulfide-Rich Sequences.Marine drugs · 2023Article
- Amyloid Fibrillation of Insulin: Amelioration Strategies and Implications for Translation.ACS pharmacology & translational science · 2022Review
- Subcellular localization of D2 receptors in the murine substantia nigra.Brain structure & function · 2022Article
- Determinants of IGF-II influencing stability, receptor binding and activation.Scientific reports · 2022Article
- Autoreactive antibodies control blood glucose by regulating insulin homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Minimizing Mitogenic Potency of Insulin Analogues Through Modification of a Disulfide Bond.Frontiers in endocrinology · 2022Article
- Pathways Linking Nicotinamide Adenine Dinucleotide Phosphate Production to Endoplasmic Reticulum Protein Oxidation and Stress.Frontiers in molecular biosciences · 2022Review
- Macrocyclization strategies for cyclic peptides and peptidomimetics.RSC medicinal chemistry · 2021Review
- Distinct states of proinsulin misfolding in MIDY.Cellular and molecular life sciences : CMLS · 2021Article
- Cysteines and Disulfide Bonds as Structure-Forming Units: Insights From Different Domains of Life and the Potential for Characterization by NMR.Frontiers in chemistry · 2020Review
- Probing the correlation between insulin activity and structural stability through introduction of the rigid A6-A11 bond.The Journal of biological chemistry · 2018Article
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Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The structural transitions required for insulin to activate its receptor and initiate regulation of glucose homeostasis are only partly understood. Here, using ring-closing metathesis, we substitute the A6-A11 disulfide bond of insulin with a rigid, non-reducible dicarba linkage, yielding two distinct stereo-isomers (cis and trans). Remarkably, only the cis isomer displays full insulin potency, rapidly lowering blood glucose in mice (even under insulin-resistant conditions). It also posseses reduced mitogenic activity in vitro. Further biophysical, crystallographic and molecular-dynamics analyses reveal that the A6-A11 bond configuration directly affects the conformational flexibility of insulin A-chain N-terminal helix, dictating insulin's ability to engage its receptor. We reveal that in native insulin, contraction of the C
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.