ArticleBioconjugate chemistry2010
Antitumor activity of ribonuclease multimers created by site-specific covalent tethering.
Article in Bioconjugate chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Anticancer Activity of Reconstituted Ribonuclease S-Decorated Artificial Viral Capsid.Chembiochem : a European journal of chemical biology · 2022Article
- Role of the Ribonuclease ONCONASE in miRNA Biogenesis and tRNA Processing: Focus on Cancer and Viral Infections.International journal of molecular sciences · 2022Review
- Biological Activities of Secretory RNases: Focus on Their Oligomerization to Design Antitumor Drugs.Frontiers in immunology · 2019Review
- Leczyme: a new candidate drug for cancer therapy.BioMed research international · 2014Review
- Sialic acid-binding lectin (leczyme) induces caspase-dependent apoptosis-mediated mitochondrial perturbation in Jurkat cells.International journal of oncology · 2013Article
- Human ribonuclease with a pendant poly(ethylene glycol) inhibits tumor growth in mice.Translational oncology · 2013Article
- Ribonuclease binase inhibits primary tumor growth and metastases via apoptosis induction in tumor cells.Cell cycle (Georgetown, Tex.) · 2013Article
- Rational design and evaluation of mammalian ribonuclease cytotoxins.Methods in enzymology · 2012Article
- Site-specific folate conjugation to a cytotoxic protein.Bioorganic & medicinal chemistry letters · 2011Article
- Site-specific PEGylation endows a mammalian ribonuclease with antitumor activity.Cancer biology & therapy · 2011Article
- Cellular uptake of ribonuclease A relies on anionic glycans.Biochemistry · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Site-specific cross-linking can generate homogeneous multimeric proteins of defined valency. Pancreatic-type ribonucleases are an especially attractive target, as their natural dimers can enter mammalian cells, evade the cytosolic ribonuclease inhibitor (RI), and exert their toxic ribonucleolytic activity. Here, we report on the use of eight distinct thiol-reactive cross-linking reagents to produce dimeric and trimeric conjugates of four pancreatic-type ribonucleases. Both the site of conjugation and, to a lesser extent, the propinquity of the monomers within the conjugate modulate affinity for RI, and hence cytotoxicity. Still, the cytotoxicity of the multimers is confounded in vitro by their increased hydrodynamic radius, which attenuates cytosolic entry. A monomeric RI-evasive variant of bovine pancreatic ribonuclease (RNase A) inhibits the growth of human prostate and lung tumors in mice. An RI-evasive trimeric conjugate inhibits tumor growth at a lower dose and with less frequent administration than does the monomer. This effect is attributable to an enhanced persistence of the trimers in circulation. On a molecular basis, the trimer is ∼300-fold more efficacious and as well tolerated as erlotinib, which is in clinical use for the treatment of lung cancer. These data encourage the development of mammalian ribonucleases for the treatment of human cancers.
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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.