Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (553 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Compounds that are designed to mimic the 3D structure of a natural peptide or protein.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Peptidomimetic.
Where it fits in the MeSH classification
- Broader topics
- Molecular Mechanisms of Pharmacological Action
Research landscape
PubMed indexes 1,824 records tagged with the MeSH heading “Peptidomimetics” (counts retrieved 2026-10-29). 658 of them (36.1%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 1,179 records.
Reviews account for 320 records (17.5%) and meta-analyses for 0. Randomized controlled trials number 4 (0.2%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 1 |
| 2010-2019 | 1,179 |
| 2020 onward | 658 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 320 | 17.5% |
| Meta-analyses | 0 | 0.0% |
| Randomized controlled trials | 4 | 0.2% |
Method: PubMed query "Peptidomimetics"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in pharmacology
Drug evidence builds in layers: laboratory pharmacology describes how a compound acts, pharmacokinetic studies describe how the body handles it, and randomized trials test whether it helps and what harms it causes. Post-marketing surveillance and observational studies reveal rarer adverse effects but cannot prove causation. This page is educational and is not a recommendation to start, stop or change any medicine; decisions about treatment belong with a qualified clinician.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes | 2015 | Review article Design not recorded in structured metadata | 508 | cc by PMID 26119925 · DOI · PMC4557054 |
| Peptidomimetic blockade of MYB in acute myeloid leukemia | 2018 | Research article Design not recorded in structured metadata | 90 | cc by PMID 29317678 · DOI · PMC5760651 |
| TEAD-YAP Interaction Inhibitors and MDM2 Binders from DNA-Encoded Indole-Focused Ugi Peptidomimetics | 2020 | Research article Design not recorded in structured metadata | 62 | cc by PMID 32537835 · DOI · PMC7689693 |
| Water-soluble β-strand peptidomimetics | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 42496002 · DOI · PMC13397914 |
Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Protein-protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable.
- Closing excerpt
- Based on this classification, the Review summarizes strategies that have been applied for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (127 words)
Protein-protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable. The identification of selective inhibitors is challenging because of the shallow and extended nature of PPI interfaces. Inhibitors can be obtained by mimicking peptide binding epitopes in their bioactive conformation. For this purpose, several strategies have been evolved to enable a projection of side chain functionalities in analogy to peptide secondary structures, thereby yielding molecules that are generally referred to as peptidomimetics. Herein, we introduce a new classification of peptidomimetics (classes A-D) that enables a clear assignment of available approaches. Based on this classification, the Review summarizes strategies that have been applied for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 26119925 · DOI · PMC4557054
Peptidomimetic blockade of MYB in acute myeloid leukemia [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Aberrant gene expression is a hallmark of acute leukemias.
- Closing excerpt
- These findings elucidate the dependence of human AML on aberrant transcriptional coactivation, and establish a pharmacologic approach for its therapeutic blockade.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (151 words)
Aberrant gene expression is a hallmark of acute leukemias. MYB-driven transcriptional coactivation with CREB-binding protein (CBP)/P300 is required for acute lymphoblastic and myeloid leukemias, including refractory MLL-rearranged leukemias. Using structure-guided molecular design, we developed a peptidomimetic inhibitor MYBMIM that interferes with the assembly of the molecular MYB:CBP/P300 complex and rapidly accumulates in the nuclei of AML cells. Treatment of AML cells with MYBMIM led to the dissociation of the MYB:CBP/P300 complex in cells, its displacement from oncogenic enhancers enriched for MYB binding sites, and downregulation of MYB-dependent gene expression, including of MYC and BCL2 oncogenes. AML cells underwent mitochondrial apoptosis in response to MYBMIM, which was partially rescued by ectopic expression of BCL2. MYBMIM impeded leukemia growth and extended survival of immunodeficient mice engrafted with primary patient-derived MLL-rearranged leukemia cells. These findings elucidate the dependence of human AML on aberrant transcriptional coactivation, and establish a pharmacologic approach for its therapeutic blockade.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29317678 · DOI · PMC5760651
TEAD-YAP Interaction Inhibitors and MDM2 Binders from DNA-Encoded Indole-Focused Ugi Peptidomimetics [3]
Abstract reading summary — source excerpts
- Opening excerpt
- DNA-encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures.
- Closing excerpt
- Selection experiments for the tumor-relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD-YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (123 words)
DNA-encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain of tryptophan plays a prominent role in key, or "hot spot", regions of protein-protein interactions. A DNA-encoded combinatorial peptoid library was designed based on the Ugi four-component reaction by employing tryptophan-mimetic indole side chains to probe the surface of target proteins. Several peptoids were synthesized on a chemically stable hexathymidine adapter oligonucleotide "hexT", encoded by DNA sequences, and substituted by azide-alkyne cycloaddition to yield a library of 8112 molecules. Selection experiments for the tumor-relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD-YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32537835 · DOI · PMC7689693
Water-soluble β-strand peptidomimetics [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Mediation of protein-protein interactions with molecules that bind strongly and selectively to one of the partners at the protein interface is a promising therapeutic strategy for myriad diseases.
- Closing excerpt
- The scaffold is conformationally preorganised for target binding in aqueous media including buffer, is readily soluble, and thus is suitable for elaboration and deployment against specific protein targets.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (152 words)
Mediation of protein-protein interactions with molecules that bind strongly and selectively to one of the partners at the protein interface is a promising therapeutic strategy for myriad diseases. One such approach is the rational design of non-peptidic scaffolds that reproduce the display of amino acid side chains from one face of a secondary structural element. We have previously disclosed proof-of principle syntheses of β-strand mimetics composed of alternating (hetero)aromatic and cyclic urea units, conformationally preorganised through dipolar repulsion in organic solvents, that are in good agreement with the i, i + 2, and i + 4 side-chain vectors of a canonical strand. Here we demonstrate sequence diversity of the approach through the incorporation of hydrophobic and hydrophilic side-chain mimics via an improved synthetic route. The scaffold is conformationally preorganised for target binding in aqueous media including buffer, is readily soluble, and thus is suitable for elaboration and deployment against specific protein targets.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42496002 · DOI · PMC13397914
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Chemical modifications designed to improve peptide stability: incorporation of non-natural amino acids, pseudo-peptide bonds, and cyclization [5]
- Research article Unusual Amino Acids in Medicinal Chemistry [6]
- Research article Annexin A1 and the Resolution of Inflammation: Modulation of Neutrophil Recruitment, Apoptosis, and Clearance [7]
- Research article Constraining cyclic peptides to mimic protein structure motifs [8]
- Research article Cell-Penetrating Peptides: Design Strategies beyond Primary Structure and Amphipathicity [9]
- Research article Peptidomimetic toolbox for drug discovery [10]
References
- Pelay-Gimeno M, Glas A, Koch O, Grossmann TN. Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes. . 2015. PMID 26119925 · DOI · PMC4557054
- Ramaswamy K, Forbes L, Minuesa G, Gindin T, Brown F, Kharas MG, et al.. Peptidomimetic blockade of MYB in acute myeloid leukemia. . 2018. PMID 29317678 · DOI · PMC5760651
- Kunig VBK, Potowski M, Akbarzadeh M, Klika Škopić M, Dos Santos Smith D, Arendt L, et al.. TEAD-YAP Interaction Inhibitors and MDM2 Binders from DNA-Encoded Indole-Focused Ugi Peptidomimetics. . 2020. PMID 32537835 · DOI · PMC7689693
- Bannister RC, Jones EF, Ross JE, Light ME, Tizzard GJ, Hamilton AD, et al.. Water-soluble β-strand peptidomimetics. . 2026. PMID 42496002 · DOI · PMC13397914
- Gentilucci L, De Marco R, Cerisoli L. Chemical modifications designed to improve peptide stability: incorporation of non-natural amino acids, pseudo-peptide bonds, and cyclization. Curr Pharm Des. 2010. PMID 20687878 · DOI
- Blaskovich MA. Unusual Amino Acids in Medicinal Chemistry. J Med Chem. 2016. PMID 27589349 · DOI
- Sugimoto MA, Vago JP, Teixeira MM, Sousa LP. Annexin A1 and the Resolution of Inflammation: Modulation of Neutrophil Recruitment, Apoptosis, and Clearance. J Immunol Res. 2016. PMID 26885535 · DOI · PMC4738713
- Hill TA, Shepherd NE, Diness F, Fairlie DP. Constraining cyclic peptides to mimic protein structure motifs. Angew Chem Int Ed Engl. 2014. PMID 25287434 · DOI
- Kalafatovic D, Giralt E. Cell-Penetrating Peptides: Design Strategies beyond Primary Structure and Amphipathicity. Molecules. 2017. PMID 29117144 · DOI · PMC6150340
- Lenci E, Trabocchi A. Peptidomimetic toolbox for drug discovery. Chem Soc Rev. 2020. PMID 32255135 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.