The Mechanism of l-Canavanine Cytotoxicity: Arginyl tRNA Synthetase as a Novel Target for Anticancer Drug Discovery

Bence, Aimee K.; Crooks, Peter A.

doi:10.1080/1475636031000152277

Cited by 53 publications

(42 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In canavanine (5) substituted oxygen atom due to its electron withdrawing nature destabilizes positive charge on the side chain guanidino group, resulting in $41 kJ mol À1 decrease in PA, comparing to arginine. This finding is consistent with results showing that structurally aberrant proteins (containing canavanine instead of arginine) do not function properly [31]. Obtained PA SC of canavanine (5) (5) could be underestimated [25].…”

Section: Arginine Homologues and Oxy-analoguessupporting

confidence: 82%

Proton affinity of several basic non-standard amino acids

Rožman

2012

Chemical Physics Letters

View full text Add to dashboard Cite

The structures and absolute proton affinities of several arginine (2-amino-3-guanidinopropionic acid, 2-amino-4-guanidinobutyric acid, homoarginine, citrulline and canavanine), histidine (1-methylhistidine and 3-methylhistidine) and lysine (2,3-diaminopropanoic acid, 2,4-diaminobutanoic acid, ornithine, 5-hydroxylysine, canaline and thialysine) homologues and analogues have been estimated using compos-ite G3MP2B3 computational protocol. For a majority of here studied non-standard amino acids the gas-phase proton affinities were established for the first time, while for the others obtained values are used to improve the accuracy of the computational and experimental proton affinities reported previ-ously. In addition, structures and proton affinities are discussed in order to rationalize their biological activity.

show abstract

Section: Arginine Homologues and Oxy-analoguessupporting

confidence: 82%

Proton affinity of several basic non-standard amino acids

Rožman

2012

Chemical Physics Letters

View full text Add to dashboard Cite

show abstract

“…It is incorporated into nascent proteins in place of L-arginine. The oxyguanidino group of L-canavanine is significantly less basic than the guanidino group of arginine; as a result, L-canavanine-containing proteins are unable to form crucial ionic interactions, resulting in altered protein structure and function that could lead to cell death (2). Interestingly, L-canavanine inhibits violacein production in C. violaceum without interfering with growth.…”

Section: Discussionmentioning

confidence: 99%

l-Canavanine Made byMedicago sativaInterferes with Quorum Sensing inSinorhizobium meliloti

et al. 2005

View full text Add to dashboard Cite

Sinorhizobium meliloti is a gram-negative soil bacterium, capable of establishing a nitrogen-fixing symbiosis with its legume host, alfalfa (Medicago sativa). Quorum sensing plays a crucial role in this symbiosis, where it influences the nodulation process and the synthesis of the symbiotically important exopolysaccharide II (EPS II). S. meliloti has three quorum-sensing systems (Sin, Tra, and Mel) that use N-acyl homoserine lactones as their quorum-sensing signal molecule. Increasing evidence indicates that certain eukaryotic hosts involved in symbiotic or pathogenic relationships with gram-negative bacteria produce quorum-sensing-interfering (QSI) compounds that can cross-communicate with the bacterial quorum-sensing system. Our studies of alfalfa seed exudates suggested the presence of multiple signal molecules capable of interfering with quorum-sensingregulated gene expression in different bacterial strains. In this work, we choose one of these QSI molecules (SWI) for further characterization. SWI inhibited violacein production, a phenotype that is regulated by quorum sensing in Chromobacterium violaceum. In addition, this signal molecule also inhibits the expression of the S. meliloti exp genes, responsible for the production of EPS II, a quorum-sensing-regulated phenotype. We identified this molecule as L-canavanine, an arginine analog, produced in large quantities by alfalfa and other legumes.

show abstract

“…Handelsman and her group showed that canavanine exuded from alfalfa seeds has the potential to affect the population biology of Bacillus cereus (31). L-Canavanine is incorporated in place of L-arginine into nascent protein chains during synthesis, resulting in altered protein structure and function and eventually leading to death of the targeted cell (7,119). In our recent work, we identified L-canavanine as a QSI compound and showed that the QSI activity is independent of its effect on bacterial growth (Table 2) (54).…”

Section: L-canavanine As a Quorum-sensing Inhibitormentioning

confidence: 99%

Messing with Bacterial Quorum Sensing

Gonzalez

Keshavan

2006

Microbiol Mol Biol Rev

376

232

View full text Add to dashboard Cite

SUMMARY Quorum sensing is widely recognized as an efficient mechanism to regulate expression of specific genes responsible for communal behavior in bacteria. Several bacterial phenotypes essential for the successful establishment of symbiotic, pathogenic, or commensal relationships with eukaryotic hosts, including motility, exopolysaccharide production, biofilm formation, and toxin production, are often regulated by quorum sensing. Interestingly, eukaryotes produce quorum-sensing-interfering (QSI) compounds that have a positive or negative influence on the bacterial signaling network. This eukaryotic interference could result in further fine-tuning of bacterial quorum sensing. Furthermore, recent work involving the synthesis of structural homologs to the various quorum-sensing signal molecules has resulted in the development of additional QSI compounds that could be used to control pathogenic bacteria. The creation of transgenic plants that express bacterial quorum-sensing genes is yet another strategy to interfere with bacterial behavior. Further investigation on the manipulation of quorum-sensing systems could provide us with powerful tools against harmful bacteria.

show abstract

The Mechanism of l-Canavanine Cytotoxicity: Arginyl tRNA Synthetase as a Novel Target for Anticancer Drug Discovery

Cited by 53 publications

References 67 publications

Proton affinity of several basic non-standard amino acids

Proton affinity of several basic non-standard amino acids

l-Canavanine Made byMedicago sativaInterferes with Quorum Sensing inSinorhizobium meliloti

Messing with Bacterial Quorum Sensing

Contact Info

Product

Resources

About