ArticleNature chemical biology2014
How proteins bind macrocycles.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers.
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.
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.
Who cites it
174 citing papers in PubMed.
- Solution Ensembles of Griselimycin Expand the Definition of Molecular Chameleonicity.Journal of medicinal chemistry · 2026Article
- Organocatalytic Enantioselective Divergent Synthesis of Pillar[5]Arenes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Generation of membrane-permeable cyclic peptides inhibiting protein-protein interaction.Nature chemical biology · 2026Article
- What Is in a Structure? Cell Permeability and Solubility of Series of Macrocycles and Linear Matched Pairs.Journal of medicinal chemistry · 2026Article
- Design of permeability-optimized target-binding macrocyclesChemical science · 2026Article
- Divergent and programmable skeletal remodeling of complex macrocycles with a small method set.Science (New York, N.Y.) · 2026Article
- Branching beyond bifunctional linkers: synthesis of macrocyclic and trivalent PROTACs.Nature protocols · 2026Review
- Orally Bioavailable Cyclin A/B RxL Inhibitors: Optimization of a Novel Class of Macrocyclic Peptides That Target E2F-High and G1-S-Checkpoint-Compromised Cancers.Journal of medicinal chemistry · 2026Article
- Conformational Trajectory of the Molecular Chameleon Grazoprevir From Formulation to Target-Bound.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Flexible molecular chameleons: structural adaptability and therapeutic applications.Frontiers in chemistry · 2026Review
- Molecular chameleons adaptability in target binding.Structural dynamics (Melville, N.Y.) · 2025Article
- A Sydnonimine-based Click-and-Release Approach to Cyclic Products.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Flexibility-tuning of dual-display DNA-encoded chemical libraries facilitates cyclic peptide ligand discovery.Nature communications · 2025Article
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.Journal of the American Chemical Society · 2025Article
- Non-spike protein inhibition of SARS-CoV-2 by natural products through the key mediator protein ORF8.Molecular biology research communications · 2025Article
- Cutting-edge Bioinformatics strategies for synthesizing Cyclotriazadisulfonamide (CADA) analogs in next-Generation HIV therapies.Scientific reports · 2024Article
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.bioRxiv : the preprint server for biology · 2024Article
- Facile Peptide Macrocyclization and Multifunctionalization via Cyclen Installation.Small methods · 2024Article
- Discovery of a Series of Macrocycles as Potent Inhibitors ofJournal of medicinal chemistry · 2024Article
- Solid-Phase Synthesis of Diverse Macrocycles by Regiospecific 2-Pyridone Formation: Scope and Applications.JACS Au · 2024Article
114 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
The potential utility of synthetic macrocycles (MCs) as drugs, particularly against low-druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of MCs for good target protein-binding activity or bioavailability. To address this knowledge gap, we analyze the binding modes of a representative set of MC-protein complexes. The results, combined with consideration of the physicochemical properties of approved macrocyclic drugs, allow us to propose specific guidelines for the design of synthetic MC libraries with structural and physicochemical features likely to favor strong binding to protein targets as well as good bioavailability. We additionally provide evidence that large, natural product-derived MCs can bind targets that are not druggable by conventional, drug-like compounds, supporting the notion that natural product-inspired synthetic MCs can expand the number of proteins that are druggable by synthetic small molecules.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.