Method for inhibiting adenylosuccinate synthetase activity in me

Details Method for inhibiting adenylosuccinate synthetase activity in me Method for inhibiting adenylosuccinate synthetase activity in me

1996-03-08

1998-11-24

Leary, Louise N.

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving hydrolase

435 21, 435 15, 435 24, 435 23, 435 4, 435 692, 435 681, 435975, 435963, 4351722, 435968, 435 29, 536 2432, 536 2431, 514 45, C12Q 134, C12Q 146, C12Q 148, C12Q 137

Patent

active

058405054

ABSTRACT:
An in vivo method for depleting mammalian cells of adenosine 5'-monophosphate (AMP) useful in the treatment of certain cancers is provided. According to the method, a population of cells is obtained from a host and assayed for loss of methylthioadenosine phosphorylase (MTAse) activity. MTAse catabolizes methylthioadenosine to adenine for endogenous salvage incorporation into the intracellular AMP pool. The preferred method for assaying loss of MTAse activity is a hybridization technique for detection of a homozygous loss of the gene which encodes MTAse. Hosts having MTAse deficient tumors are treated with a therapeutically effective amount of an agent which inhibits the activity of adenylsuccinate synthetase, which converts inosine 5'-monophosphate to AMP, thus depleting the tumor cells of substrates for de novo AMP production. L-alanosine is the preferred ASS inhibitory agent for use in the method of the invention.

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Willis et al; Adv. Exp. Med. Biol.; vol. 122B, pp. 237-241; 1980.
Guicherit et al; J. Biol. Chem; vol. 269, No. 6, pp. 4488-4496, 1994.

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