ArticleThe Journal of biological chemistry2010
Supramolecular protein engineering: design of zinc-stapled insulin hexamers as a long acting depot.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 29 citations in OpenAlex.
- Crosstalk between zinc and free fatty acids in plasma.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Stapled Peptides Inhibitors: A New Window for Target Drug Discovery.Computational and structural biotechnology journal · 2019Review
- An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein.The Journal of biological chemistry · 2018Article
- Design of non-standard insulin analogs for the treatment of diabetes mellitus.Current diabetes reports · 2012Review
- Chitosan-zinc-insulin complex incorporated thermosensitive polymer for controlled delivery of basal insulin in vivo.Journal of controlled release : official journal of the Controlled Release Society · 2012Article
- α-Helical element at the hormone-binding surface of the insulin receptor functions as a signaling element to activate its tyrosine kinase.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Materials for diabetes therapeutics.Advanced healthcare materials · 2012Review
- Engineering a zinc binding site into the de novo designed protein DS119 with a βαβ structure.Protein & cell · 2011Article
- Insulin analogs for the treatment of diabetes mellitus: therapeutic applications of protein engineering.Annals of the New York Academy of Sciences · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Bottom-up control of supramolecular protein assembly can provide a therapeutic nanobiotechnology. We demonstrate that the pharmacological properties of insulin can be enhanced by design of "zinc staples" between hexamers. Paired (i, i+4) His substitutions were introduced at an alpha-helical surface. The crystal structure contains both classical axial zinc ions and novel zinc ions at hexamer-hexamer interfaces. Although soluble at pH 4, the combined electrostatic effects of the substitutions and bridging zinc ions cause isoelectric precipitation at neutral pH. Following subcutaneous injection in a diabetic rat, the analog effected glycemic control with a time course similar to that of long acting formulation Lantus. Relative to Lantus, however, the analog discriminates at least 30-fold more stringently between the insulin receptor and mitogenic insulin-like growth factor receptor. Because aberrant mitogenic signaling may be associated with elevated cancer risk, such enhanced specificity may improve safety. Zinc stapling provides a general strategy to modify the pharmacokinetic and biological properties of a subcutaneous protein depot.
Indexed as
Identifiers
What OpenQuestion holds
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.