Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1997-01-21
1998-11-03
Carlson, Karen C.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
435325, 435366, 435372, 536 235, 530350, C12P 2106, C12N 522, C12N 1512, C07K 14435
Patent
active
058306978
ABSTRACT:
A mutated form of human P-glycoprotein (mdr1.DELTA.F335/336) is identified, consisting of a single or double codon deletion (Phe335 and/or 336) in the TM region of P-gp. The mdr1.DELTA.F335/336 encoded P-glycoprotein is characterized by an altered spectrum of cross-reactivity to cytotoxins and resistance to modulation by cyclosporins, with a loss of the capacity to bind or transport cyclosporine, PSC 833, and vinblastine. These data demonstrate that cyclosporine, PSC 833, vinblastine, Rh-123, and dactinomycin share at least one binding domain on, which plays an important role in the interaction of P-gp with modulators. The nucleic acid compositions encoding mdr1.DELTA.F335/336 find use in gene therapy to transfer modulator-resistant multidrug resistance into transfected cells; to produce the encoded protein for functional mapping studies, and in studying associated physiological pathways.
REFERENCES:
Loo et al. J. Biol. Chem. 268: 19965-19972 1993.
Chen et al Proc. Am. Assoc. Cancer Res 37:323 Mar. 1996.
DuMontet et al Proc. Am Assoc. Cancer Res 37:329 Mar. 1996.
Chen Gang
Sikic Branimir I.
Carlson Karen C.
Sherwood Pamela J.
The Board of Trustees of the Leland Stanford Junior University
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