ArticleBiochemistry2011
Arginine residues are more effective than lysine residues in eliciting the cellular uptake of onconase.
Article in Biochemistry, 2011. 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, 27 citations in OpenAlex.
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- Resurfacing receptor binding domain of Colicin N to enhance its cytotoxic effect on human lung cancer cells.Computational and structural biotechnology journal · 2021Article
- Biological Activities of Secretory RNases: Focus on Their Oligomerization to Design Antitumor Drugs.Frontiers in immunology · 2019Review
- Review
- ROMP- and RAFT-Based Guanidinium-Containing Polymers as Scaffolds for Protein Mimic Synthesis.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
- An Evolved RNA Recognition Motif That Suppresses HIV-1 Tat/TAR-Dependent Transcription.ACS chemical biology · 2016Article
- Scratching the Surface: Resurfacing Proteins to Endow New Properties and Function.Cell chemical biology · 2016Review
- Fluorescence correlation spectroscopy reveals highly efficient cytosolic delivery of certain penta-arg proteins and stapled peptides.Journal of the American Chemical Society · 2015Article
- Optimization of the cyclotide framework to improve cell penetration properties.Frontiers in pharmacology · 2015Article
- Sialyl-glycoconjugates in cholesterol-rich microdomains of P388 cells are the triggers for apoptosis induced by Rana catesbeiana oocyte ribonuclease.Glycoconjugate journal · 2014Article
- Cationic membrane peptides: atomic-level insight of structure-activity relationships from solid-state NMR.Amino acids · 2013Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Onconase is an amphibian member of the pancreatic ribonuclease family of enzymes that is in clinical trials for the treatment of cancer. Onconase, which has an abundance of lysine residues, is internalized by cancer cells through endocytosis in a mechanism similar to that of cell-penetrating peptides. Here, we compare the effect of lysine versus arginine residues on the biochemical attributes necessary for Onconase to elicit its cytotoxic activity. In the variant R-Onconase, 10 of the 12 lysine residues in Onconase are replaced with arginine, leaving only the two active-site lysines intact. Cytometric assays quantifying internalization showed a 3-fold increase in the internalization of R-Onconase compared with Onconase. R-Onconase also showed greater affinity for heparin and a 2-fold increase in ribonucleolytic activity. Nonetheless, arginine substitution endowed only a slight increase in toxicity toward human cancer cells. Analysis of denaturation induced with guanidine-HCl showed that R-Onconase has less conformational stability than does the wild-type enzyme; moreover, R-Onconase is more susceptible to proteolytic degradation. These data indicate that arginine residues are more effective than lysine in eliciting cellular internalization but can compromise other aspects of protein structure and function.
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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.