Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1995-08-18
1999-02-16
Adams, Donald E.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
435 691, 4351723, C07K 100, C12P 2106, C12N 1500
Patent
active
058722130
ABSTRACT:
Upon entry into a host cell, retroviruses direct the reverse transcription of the viral RNA genome and the establishment of an integrated proviral DNA. The retroviral integrase protein (IN) is responsible for the insertion of the viral DNA into host chromosomal targets. The IN catalyzes two specific biochemical reactions: (i) cleavage of the 3'termini of the viral DNA to produce 3'-OH ends, and (ii) joining of the two newly generated 3'-termini to the 5'-phosphates on each strand of the target sequence in a concerted strand-transfer reaction. The yeast two-hybrid system was used to identify a novel human gene product, herein designated integrase interactor 1 or INI-1, that binds tightly to the human immunodeficiency virus type 1 (HIV-1) integrase in vitro. Approximately 10.sup.6 complementary DNAs (cDNAs) of the HL60 macrophage-monocytic cell line were expressed as GAL4AC (activation domain) fusions and tested for coactivation of a reporter gene together with a GAL4DB (DNA binding) IN fusion. Overlapping cDNA clones were identified and their nucleotide sequences ascertained. Nucleotide sequence analysis revealed that INI-1 displays limited amino acid homology to the yeast SNF5 protein, a transcriptional activator required for high-level expression of many disparate cellular genes. The INI-1 gene product will prove useful for the generation of biochemical reagents and the development novel HIV-1 antiviral agents.
REFERENCES:
Lewin, Genes IV, Oxford University Press, New York, 1990, pp. 482-495 and 617-621.
Goff Stephen P.
Kalpana Ganjam V.
Adams Donald E.
Parkin Jeffrey S.
The Trustees of Columbia University in the City of New York
White John P.
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