23K protein with binding specificity for queuine

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues

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Details

530412, 530413, 530851, C07K 1500, C07K 318

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active

053129008

ABSTRACT:
The invention generally relates to the discovery of a 23 kD protein, designated herein as Queb, that has specific binding affinity for the purine base Queuine. The invention particularly relates to polypeptides having specific binding reactivity with Queuine and methods of using such polypeptides to purify Queuine and Queuine-containing substances. The invention also relates to antibodies having specific reactivity with Queuine or Queb. Methods for determining the presence and concentration of Queuine and Queb are also provided as well as methods for the diagnosis of a pathological disease or prognosis of a patient having a disease associated with Queuine, Queuine-containing substances such as Queuine-tRNA, or Queb. Kits useful for performing the methods of the present invention are also provided.

REFERENCES:
patent: 4571423 (1986-02-01), Nomura et al.
patent: 4595530 (1986-06-01), Nishimura et al.
Kuchino et al "Preparation and Characterization of Monoclonal Antibodies for the Modified Base Queine" Proc. Jnp. Acad. 63 1987, pp. 393-396.
Kuchino et al "Monoclonal Antibodies to Queine" Nuc Acid Res 16 1985 221-223.
Harlow et al "Antibodies A Laboratory Manual" Cold Spring Harbor Lab, 1988, p. 313.
Kasai et al., Distribution of the modified nucleoside Q and its derivatives in animal and plant transfer RNA's. Nucl. Acids Res. 2:1931-1939 (1975).
Katze et al., Queuine, a modified base incorporated posttranscriptionally into eukaryotic transfer RNA: wide distribution in nature. Science 216:55-56 (1982).
Okada et al., Novel mechanism of post-transcriptional modification of tRNA. J. Biol. Chem. 254:3067-3073 (1978).
Okada and Nishimura, Isolation and characterization of a guanine insertion enzyme, a specified tRNA transglycosylase, from Escherichia coli. J. Biol. Chem. 254:3061-3066 (1978).
French et al., Queuine, a tRNA anticodon wobble base, maintains the proliferative and pluripotent potential of HL-60 cells in the presence of the differentiating agent 6-thioguanine. Proc. Natl. Acad. Sci. USA 38:370-374 (1991).
Langgut and Kersten, The deazaguanine-derivative, queuine, affects cell proliferation, protein phosphorylation and the expression of the proto oncogenes c-fos and c-myc in Hela cells. FEBS 265:33-36 (1990).
Randerath et al., Speicific lack of the hypermodified nucleoside, queuosine, in hepatoma mitochondrial aspartate transfer RNA and its possible biological significance. Cancer Res. 44:1167-1171 (1984).
Bienz et al., Wild-type tRNA.sup.Tyr reads the TMV RNA stop codon, but Q base-modified tRNA.sup.Tyr does not. Nature 294:188-190 (1981).
Emmerich et al., Relationship of queuine-lacking transfer RNAs to the grade of malignancy in human leukemias and lymphomas. Cancer Res. 43:4308-4314 (1985).
Katz and Farkas, A factor in serum and amniotic fluid is a substrate for the tRNA-modifying enzyme tRNA-guanine transferase. Proc. Natl. Acad. Sci. USA 76:3271-3275 (1979).
Singhal, Queuine: an addendum. Progress in Nucleic Acids Research and Molecular Biology 28:75-80.
Nishimura et al., Characterization and analysis of oncofetal tRNA and its possible application for cancer diagnosis and therapy. Recent Results in Cancer Research. 84:401-412 (1983).
Akimoto et al., Queuine analogues: their synthesis and inhibition of growth of mouse L5178Y cells in vitro. J. Med. Chem. 29:1749-1753 (1986).

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