CHARACTERIZATION OF GROWTH AND METAL-BINDING CONSTITUENTS OF TWO CITRUS CELL CULTURE LINES

Citrus blight is an extremely complex decline disorder of unknown etiology, Zinc accumulates in the phloem of the tree 40-50 cm above the bud union 1-3 years prior to visible symptoms of blight (foliage wilt and twig dieback). This is accompanied by Zn deficits in the leaves. A Zn-binding peptide (ZBP) purified from citrus phloem tissue accounts for a symptomatic redistribution of Zn from the canopy to the trunk phloem. ZBP is found in blight and healthy trees and is therefore a normal component of cellular metabolism. To further understand ZBP's role in metabolism two citrus cell culture lines which were selected based on their susceptibility to blight have been characterized as to their growth under Zn treatments as well as Cu and Cd. In addition, their complement of metal-binding constituents is being determined.

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Synthesis and characterization of a metal-binding peptide fragment of human carbonic anhydrase B

Bioorganic Chemistry ◽

10.1016/0045-2068(78)90027-5 ◽

1978 ◽

Vol 7 (3) ◽

pp. 313-332 ◽

Cited By ~ 1

Author(s):

Rebecca L. Chan ◽

Nget Hong Tan ◽

E.T. Kaiser

Keyword(s):

Carbonic Anhydrase ◽

Metal Binding ◽

Synthesis And Characterization ◽

Peptide Fragment ◽

Binding Peptide ◽

Carbonic Anhydrase B ◽

Human Carbonic Anhydrase

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Targeting IDH Mutations in AML: Wielding the Double-edged Sword of Differentiation

Current Cancer Drug Targets ◽

10.2174/1568009620666200424145622 ◽

2020 ◽

Vol 20 (7) ◽

pp. 490-500 ◽

Cited By ~ 1

Author(s):

Justin S. Becker ◽

Amir T. Fathi

Keyword(s):

Genome Structure ◽

Cellular Metabolism ◽

Standard Of Care ◽

Competitive Inhibitor ◽

Driver Mutations ◽

New Class ◽

Regulatory Enzymes ◽

Idh Mutations ◽

Genomic Characterization

The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2). These enzymes are constitutive mediators of basic cellular metabolism, but their mutated forms in cancer synthesize an abnormal metabolite, 2- hydroxyglutarate, that in turn acts as a competitive inhibitor of multiple gene regulatory enzymes. As a result, leukemic IDH mutations cause changes in genome structure and gene activity, culminating in an arrest of normal myeloid differentiation. These discoveries have motivated the development of a new class of selective small molecules with the ability to inhibit the mutant IDH enzymes while sparing normal cellular metabolism. These agents have shown promising anti-leukemic activity in animal models and early clinical trials, and are now entering Phase 3 study. This review will focus on the growing preclinical and clinical data evaluating IDH inhibitors for the treatment of IDH-mutated AML. These data suggest that inducing cellular differentiation is central to the mechanism of clinical efficacy for IDH inhibitors, while also mediating toxicity for patients who experience IDH Differentiation Syndrome. Ongoing trials are studying the efficacy of IDH inhibitors in combination with other AML therapies, both to evaluate potential synergistic combinations as well as to identify the appropriate place for IDH inhibitors within existing standard-of-care regimens.

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