ArticleProceedings of the National Academy of Sciences of the United States of America2012
Heterobivalent ligands target cell-surface receptor combinations in vivo.
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 36 papers.
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Who cites it
36 citing papers in PubMed.
- Surface plasmon resonance microscopy reveals N-glycosylation driven modulation of affinity and avidity of ErbB receptors in whole single pancreatic cancer cells.Glycobiology · 2025Article
- Organelle-Specific Smart Supramolecular Materials for Bioimaging and Theranostics Application.Topics in current chemistry (Cham) · 2024Review
- Development and Evaluation of a Peptide Heterodimeric Tracer Targeting CXCR4 and Integrin αPharmaceutics · 2022Article
- Engineered protein-small molecule conjugates empower selective enzyme inhibition.Cell chemical biology · 2022Article
- A Remote Secondary Binding Pocket Promotes Heteromultivalent Targeting of DC-SIGN.Journal of the American Chemical Society · 2021Article
- Transferrin receptor 1 targeted optical imaging for identifying glioma margin in mouse models.Journal of neuro-oncology · 2020Article
- Photo-Click-Facilitated Screening Platform for the Development of Hetero-Bivalent Agents with High Potency.The Journal of organic chemistry · 2020Article
- Nano-scientific Application of Atomic Force Microscopy in Pathology: from Molecules to Tissues.International journal of medical sciences · 2020Review
- Single-Molecule Force Measurement Guides the Design of Multivalent Ligands with Picomolar Affinity.Angewandte Chemie (International ed. in English) · 2019Article
- Developing a Biased Unmatched Bivalent Ligand (BUmBL) Design Strategy to Target the GPCR Homodimer Allosteric Signaling (cAMP over β-Arrestin 2 Recruitment) Within the Melanocortin Receptors.Journal of medicinal chemistry · 2019Article
- Design and Evaluation of Heterobivalent PAR1-PAR2 Ligands as Antagonists of Calcium Mobilization.ACS medicinal chemistry letters · 2019Article
- Multivalent activation of GLP-1 and sulfonylurea receptors modulates β-cell second-messenger signaling and insulin secretion.American journal of physiology. Cell physiology · 2019Article
- Dual-modal in vivo fluorescence and photoacoustic imaging using a heterodimeric peptide.Chemical communications (Cambridge, England) · 2018Article
- Programmable Multivalent DNA-Origami Tension Probes for Reporting Cellular Traction Forces.Nano letters · 2018Article
- Multiplexed Targeting of Barrett's Neoplasia with a Heterobivalent Ligand: Imaging Study on Mouse Xenograft in Vivo and Human Specimens ex Vivo.Journal of medicinal chemistry · 2018Article
- Utilizing Peptide Ligand GPCRs to Image and Treat Pancreatic Cancer.Biomedicines · 2018Review
- Homo- and Heterodimerization of Proteins in Cell Signaling: Inhibition and Drug Design.Advances in protein chemistry and structural biology · 2018Review
- Cell-surface marker discovery for lung cancer.Oncotarget · 2017Article
- Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- A Direct in Vivo Comparison of the Melanocortin Monovalent Agonist Ac-His-DPhe-Arg-Trp-NHACS chemical neuroscience · 2017Article
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Authors and funding
9 authors.
Funding
Abstract
A challenge in tumor targeting is to deliver payloads to cancers while sparing normal tissues. A limited number of antibodies appear to meet this challenge as therapeutics themselves or as drug-antibody conjugates. However, antibodies suffer from their large size, which can lead to unfavorable pharmacokinetics for some therapeutic payloads, and that they are targeted against only a single epitope, which can reduce their selectivity and specificity. Here, we propose an alternative targeting approach based on patterns of cell surface proteins to rationally develop small, synthetic heteromultivalent ligands (htMVLs) that target multiple receptors simultaneously. To gain insight into the multivalent ligand strategy in vivo, we have generated synthetic htMVLs that contain melanocortin (MSH) and cholecystokinin (CCK) pharmacophores that are connected via a fluorescent labeled, rationally designed synthetic linker. These ligands were tested in an experimental animal model containing tumors that expressed only one (control) or both (target) MSH and CCK receptors. After systemic injection of the htMVL in tumor-bearing mice, label was highly retained in tumors that expressed both, compared with one, target receptors. Selectivity was quantified by using ex vivo measurement of Europium-labeled htMVL, which had up to 12-fold higher specificity for dual compared with single receptor expressing cells. This proof-of-principle study provides in vivo evidence that small, rationally designed bivalent htMVLs can be used to selectively target cells that express both, compared with single complimentary cell surface targets. These data open the possibility that specific combinations of targets on tumors can be identified and selectively targeted using htMVLs.
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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.