Evidence map›Paper›PMID 36697672›Full record

ArticleCommunications chemistry2022

Binary combinatorial scanning reveals potent poly-alanine-substituted inhibitors of protein-protein interactions.

Xiyun Ye, Yen-Chun Lee, Zachary P Gates, Yingjie Ling, Jennifer C Mortensen, Fan-Shen Yang, Yu-Shan Lin, Bradley L Pentelute

Open access · goldAbstract read
In one paragraph

Article in Communications chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

10 citing papers in PubMed, 27 citations in OpenAlex.

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  4. Insight into Protein Engineering: FromCurrent pharmaceutical design · 2025
    Review
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  10. Review
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

8 authors at 5 institutions in 3 countries.

Xiyun Ye *Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-5342-9244
Yen-Chun Lee *Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-6961-6992
Zachary P GatesDepartment of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Yingjie LingDepartment of Chemistry, Tufts University, 62 Talbot Avenue, Medford, MA, 02155, USA.
Jennifer C MortensenDepartment of Chemistry, Tufts University, 62 Talbot Avenue, Medford, MA, 02155, USA.ORCID http://orcid.org/0000-0001-8080-337X
Fan-Shen YangDepartment of Chemistry and Frontier Research Center on Fundamental and Applied Sciences and Matters, National Tsing Hua University, 101, Sec. 2, Guang-Fu Road, Hsinchu, 300, Taiwan.
Yu-Shan LinDepartment of Chemistry, Tufts University, 62 Talbot Avenue, Medford, MA, 02155, USA.
Bradley L PenteluteDepartment of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. blp@mit.edu.ORCID http://orcid.org/0000-0002-7242-801X
Tufts University · USMassachusetts Institute of Technology · USAgency for Science, Technology and Research · SGBroad Institute · USNational Tsing Hua University · TW

Funding

Tufts IRACDAK12GM133314 · NIGMS · TUFTS UNIVERSITY BOSTON · PI CLAIRE L MOORE, Jamie Lynn Maguire · 2019 to 2026
$8.4M
Understanding and Designing Cyclic PeptidesR01GM124160 · NIGMS · TUFTS UNIVERSITY MEDFORD · PI Yu-Shan Lin · 2017 to 2026
$3.2M
Acquisition of Octet Biolayer Interferometry system for MIT biophysics facilityS10OD016326 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI IMPERIALI, BARBARA · 2014 to 2014
$180k
NIGMS NIH HHS K12 GM133314NIGMS NIH HHS R01 GM124160NIH HHS S10 OD016326
6 · The paper itself

Abstract

Establishing structure-activity relationships is crucial to understand and optimize the activity of peptide-based inhibitors of protein-protein interactions. Single alanine substitutions provide limited information on the residues that tolerate simultaneous modifications with retention of biological activity. To guide optimization of peptide binders, we use combinatorial peptide libraries of over 4,000 variants-in which each position is varied with either the wild-type residue or alanine-with a label-free affinity selection platform to study protein-ligand interactions. Applying this platform to a peptide binder to the oncogenic protein MDM2, several multi-alanine-substituted analogs with picomolar binding affinity were discovered. We reveal a non-additive substitution pattern in the selected sequences. The alanine substitution tolerances for peptide ligands of the 12ca5 antibody and 14-3-3 regulatory protein are also characterized, demonstrating the general applicability of this new platform. We envision that binary combinatorial alanine scanning will be a powerful tool for investigating structure-activity relationships.

Identifiers

PMID36697672
PMCPMC9814900
OpenAlexW4306165746

What OpenQuestion holds

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Registered trials

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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.