Evidence map›Paper›PMID 29090903›Full record

ArticleACS chemical biology2018

Chemically Precise Glycoengineering Improves Human Insulin.

Xiaoyang Guan, Patrick K Chaffey, Xiuli Wei, Daniel R Gulbranson, Yuan Ruan, Xinfeng Wang, Yaohao Li, Yan Ouyang, Liqun Chen, Chen Zeng and 5 more

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 19% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 43 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 2 countries.

Xiaoyang GuanDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.
Patrick K ChaffeyDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.
Xiuli WeiProtein and Peptide Pharmaceutical Laboratory, Institute of Biophysics Chinese Academy of Sciences , 15 Datun Road, Beijing 100101, People's Republic of China.
Daniel R GulbransonDepartment of Molecular, Cellular, and Developmental Biology, University of Colorado , Boulder, Colorado 80303, United States.
Yuan RuanDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.
Xinfeng WangDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.ORCID 0000-0002-6399-1011
Yaohao LiDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.
Yan OuyangDepartment of Molecular, Cellular, and Developmental Biology, University of Colorado , Boulder, Colorado 80303, United States.
Liqun ChenDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.
Chen ZengDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.
Theo N KoelschDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.
Amy H TranDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.
Wei LiangProtein and Peptide Pharmaceutical Laboratory, Institute of Biophysics Chinese Academy of Sciences , 15 Datun Road, Beijing 100101, People's Republic of China.
Jingshi ShenDepartment of Molecular, Cellular, and Developmental Biology, University of Colorado , Boulder, Colorado 80303, United States.
Zhongping TanDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.ORCID 0000-0002-9302-150X
University of Colorado Boulder · USChinese Academy of Sciences · CN

Funding

Regulatory Mechanisms of GLUT4 ExocytosisR01DK095367 · NIDDK · UNIVERSITY OF COLORADO · PI SHEN, JINGSHI · 2013 to 2017
$1.7M
Regulatory Mechanisms of GLUT4 ExocytosisR56DK095367 · NIDDK · UNIVERSITY OF COLORADO · PI SHEN, JINGSHI · 2012 to 2018
$598k
NIDDK NIH HHS R01 DK095367NIDDK NIH HHS R56 DK095367
6 · The paper itself

Abstract

Diabetes is a leading cause of death worldwide and results in over 3 million annual deaths. While insulin manages the disease well, many patients fail to comply with injection schedules, and despite significant investment, a more convenient oral formulation of insulin is still unavailable. Studies suggest that glycosylation may stabilize peptides for oral delivery, but the demanding production of homogeneously glycosylated peptides has hampered transition into the clinic. We report here the first total synthesis of homogeneously glycosylated insulin. After characterizing a series of insulin glycoforms with systematically varied O-glycosylation sites and structures, we demonstrate that O-mannosylation of insulin B-chain Thr27 reduces the peptide's susceptibility to proteases and self-association, both critical properties for oral dosing, while maintaining full activity. This work illustrates the promise of glycosylation as a general mechanism for regulating peptide activity and expanding its therapeutic use.

Indexed as

AnimalsCell LineDrug DesignGlucose Transporter Type 4HumansInsulinMiceProtein EngineeringStructure-Activity RelationshipThreonineGlucose Transporter Type 4Insulininsulin, glycosylatedSlc2a4 protein, mouseThreonine

Identifiers

PMID29090903
PMCPMC6287623
OpenAlexW2766882852

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.