Evidence map›Paper›PMID 26715336›Full record

ArticleChembiochem : a European journal of chemical biology2016

Efficient Total Chemical Synthesis of (13) C=(18) O Isotopomers of Human Insulin for Isotope-Edited FTIR.

Balamurugan Dhayalan, Ann Fitzpatrick, Kalyaneswar Mandal, Jonathan Whittaker, Michael A Weiss, Andrei Tokmakoff, Stephen B H Kent

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chembiochem : a European journal of chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

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  7. Novel protein science enabled by total chemical synthesis.Protein science : a publication of the Protein Society · 2019
    Review
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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

7 authors.

Balamurugan DhayalanDepartment of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA.
Ann FitzpatrickDepartment of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA.
Kalyaneswar MandalDepartment of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA.
Jonathan WhittakerDepartment of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Michael A WeissDepartment of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Andrei TokmakoffDepartment of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. tokmakoff@uchicago.edu.
Stephen B H KentDepartment of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. skent@uchicago.edu.

Funding

Y-FAMILY POLYMERASES AND CO-FACTORS IN TRANSLESION REPLICATIONP41RR015301 · NCRR · CORNELL UNIVERSITY ITHACA · PI DONG, ZIGANG · 2001 to 2011
$28.2M
Non-Standard Protein Design in Molecular Endocrinology: Insulin and GlucagonR01DK040949 · NIDDK · UNIVERSITY OF CHICAGO · PI CHERRINGTON, ALAN D, GEORGIADIS, MILLIE M · 1989 to 2024
$8.4M
Design, Total Synthesis & Properties of Novel Chemical Analogs of Human InsulinR01DK089934 · NIDDK · UNIVERSITY OF CHICAGO · PI KENT, STEPHEN B.H. · 2010 to 2013
$1.5M
LIGAND INDEPENDENT T3 RECEPTOR ACTIONF32DK008993 · NIDDK · UNIVERSITY OF MINNESOTA TWIN CITIES · PI FANG, SEAN · 1993 to 1995
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NCRR NIH HHS P41 RR015301NCRR NIH HHS RR-15301NIDDK NIH HHS F32 DK008993NIDDK NIH HHS R01 DK040949NIDDK NIH HHS R01 DK089934PHS HHS R01K08993
6 · The paper itself

Abstract

Isotope-edited two-dimensional Fourier transform infrared spectroscopy (2 D FTIR) can potentially provide a unique probe of protein structure and dynamics. However, general methods for the site-specific incorporation of stable (13) C=(18) O labels into the polypeptide backbone of the protein molecule have not yet been established. Here we describe, as a prototype for the incorporation of specific arrays of isotope labels, the total chemical synthesis-via a key ester insulin intermediate-of 97 % enriched [(1-(13) C=(18) O)Phe(B24) ] human insulin: stable-isotope labeled at a single backbone amide carbonyl. The amino acid sequence as well as the positions of the disulfide bonds and the correctly folded structure were unambiguously confirmed by the X-ray crystal structure of the synthetic protein molecule. In vitro assays of the isotope labeled [(1-(13) C=(18) O)Phe(B24) ] human insulin showed that it had full insulin receptor binding activity. Linear and 2 D IR spectra revealed a distinct red-shifted amide I carbonyl band peak at 1595 cm(-1) resulting from the (1-(13) C=(18) O)Phe(B24) backbone label. This work illustrates the utility of chemical synthesis to enable the application of advanced physical methods for the elucidation of the molecular basis of protein function.

Indexed as

Amino Acid SequenceCarbon IsotopesHumansInsulinMolecular Sequence DataOxygen IsotopesSpectroscopy, Fourier Transform InfraredCarbon IsotopesInsulinOxygen Isotopeschemical protein synthesishuman insulinIR spectroscopyisotopic labelingnative chemical ligation

Identifiers

PMID26715336
PMCPMC5477233

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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.