Evidence map›Paper›PMID 37587780›Full record

ArticleAngewandte Chemie (International ed. in English)2023

Harnessing Aromatic-Histidine Interactions through Synergistic Backbone Extension and Side Chain Modification.

Zhen Yu, Dale F Kreitler, Yin Ting T Chiu, Ruiwen Xu, Austin T Bruchs, Craig A Bingman, Samuel H Gellman

Open access · bronzeAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 41% 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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

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 at 2 institutions in 1 country.

Zhen YuDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.ORCID 0000-0003-2092-9960
Dale F KreitlerNational Synchrotron Light Source II, Brookhaven National Laboratory, Upton, New York, 11973, USA.ORCID 0000-0003-4758-7913
Yin Ting T ChiuDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.ORCID 0000-0001-5449-8391
Ruiwen XuDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.ORCID 0000-0001-8477-2718
Austin T BruchsDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.ORCID 0000-0003-0819-3639
Craig A BingmanDepartment of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.ORCID 0000-0002-3073-5089
Samuel H GellmanDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.ORCID 0000-0001-5617-0058
University of Wisconsin–Madison · USBrookhaven National Laboratory · US

Funding

X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Sean McSweeney · 2019 to 2026
$38.6M
Protein Recognition by Peptidic FoldamersR01GM056414 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GELLMAN, SAMUEL H. · 1997 to 2023
$6.5M
MALDI TOF/TOF Mass SpectrometerS10RR024601 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI GELLMAN, SAMUEL H. · 2008 to 2008
$376k
NCRR NIH HHS S10 RR024601NIGMS NIH HHS P30 GM133893NIGMS NIH HHS R01 GM056414
6 · The paper itself

Abstract

Peptide engineering efforts have delivered drugs for diverse human diseases. Side chain alteration is among the most common approaches to designing new peptides for specific applications. The peptide backbone can be modified as well, but this strategy has received relatively little attention. Here we show that new and favorable contacts between a His side chain on a target protein and an aromatic side chain on a synthetic peptide ligand can be engineered by rational and coordinated side chain modification and backbone extension. Side chain modification alone was unsuccessful. Binding measurements, high-resolution structural studies and pharmacological outcomes all support the synergy between backbone and side chain modification in engineered ligands of the parathyroid hormone receptor-1, which is targeted by osteoporosis drugs. These results should motivate other structure-based designs featuring coordinated side chain modification and backbone extension to enhance the engagement of peptide ligands with target proteins.

Indexed as

HistidinePeptidesAmino Acid SequenceHumansLigandsProteinsHistidineLigandsPeptidesProteinsBackbone ModificationG-Protein-Coupled ReceptorsHistidineProtein-Peptide Interactionsβ-Amino Acids

Identifiers

PMID37587780
PMCPMC10668598
OpenAlexW4385897333

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.