ArticleProceedings of the National Academy of Sciences of the United States of America2012
Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 143 citations in OpenAlex.
- De Novo Design and Directed Evolution Refinement of Mirror-Image Protein Binders Targeting Interleukin-4.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advancing protein engineering via organic chemistry.Communications chemistry · 2026Review
- Protein Structure Determination by Racemic and Quasi-Racemic X-Ray Crystallography.Chembiochem : a European journal of chemical biology · 2026Review
- Mirror-Peptidizer: In Silico Mirror-Image Screening Enables De Novo Design of D-Peptide Binders without D-Protein Synthesis.Research (Washington, D.C.) · 2026Article
- Discovery of d‑Miniprotein Inhibitors of PD-1/PD-L1 Interaction via Mirror-Image Phage Display against Synthetic d‑PD‑1.JACS Au · 2025Article
- Rapid clearance of achiral small-molecule drugs using de novo-designed proteins and their cyclic and mirror-image variants.Nature biomedical engineering · 2025Article
- Advances in the chemical synthesis of human proteoforms.Science China. Life sciences · 2025Review
- Functional Ambidexterity of an Ancient Nucleic Acid-Binding Domain.Angewandte Chemie (International ed. in English) · 2025Article
- Chemical Protein Engineering: Backbone Cyclization Rescues Folding of a 183-Residue Truncated Domain of Malaria Parasite Protein PfAMA1.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- The Potential of Peptide-Based Inhibitors in Disrupting Protein-Protein Interactions for Targeted Cancer Therapy.International journal of molecular sciences · 2025Review
- Generating a mirror-image monobody targeting MCP-1 via TRAP display and chemical protein synthesis.Nature communications · 2024Article
- Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase.Nature communications · 2024Article
- Accurate de novo design of heterochiral protein-protein interactions.Cell research · 2024Article
- Mirror-image trypsin digestion and sequencing of D-proteins.Nature chemistry · 2024Article
- Mirror-image ligand discovery enabled by single-shot fast-flow synthesis of D-proteins.Nature communications · 2024Article
- A cysteine-specific solubilizing tag strategy enables efficient chemical protein synthesis of difficult targets.Chemical science · 2024Article
- Design and Synthesis of Monobody Variants with Low Immunogenicity.ACS medicinal chemistry letters · 2023Article
- Synthesis and applications of mirror-image proteins.Nature reviews. Chemistry · 2023Review
- D-Peptide and D-Protein Technology: Recent Advances, Challenges, and Opportunities.Chembiochem : a European journal of chemical biology · 2023Review
- Synthesis of the l- and d-SH2 domain of the leukaemia oncogene Bcr-Abl.RSC chemical biology · 2022Article
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 at 3 institutions in 2 countries.
Funding
Abstract
Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically synthesized D- and L- forms of the protein ligand showed reciprocal chiral specificity in surface plasmon resonance binding experiments: The L-protein ligand bound only to D-VEGF-A, whereas the D-protein ligand bound only to L-VEGF-A. The D-protein ligand, but not the L-protein ligand, inhibited the binding of natural VEGF(165) to the VEGFR1 receptor. Racemic protein crystallography was used to determine the high resolution X-ray structure of the heterochiral complex consisting of {D-protein antagonist + L-protein form of VEGF-A}. Crystallization of a racemic mixture of these synthetic proteins in appropriate stoichiometry gave a racemic protein complex of more than 73 kDa containing six synthetic protein molecules. The structure of the complex was determined to a resolution of 1.6 Å. Detailed analysis of the interaction between the D-protein antagonist and the VEGF-A protein molecule showed that the binding interface comprised a contact surface area of approximately 800 Å(2) in accord with our design objectives, and that the D-protein antagonist binds to the same region of VEGF-A that interacts with VEGFR1-domain 2.
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.