Inhibition of lactate production by pyruvate adducts

Details Inhibition of lactate production by pyruvate adducts Inhibition of lactate production by pyruvate adducts

1987-02-20

1990-08-21

Wax, Robert A.

Chemistry: molecular biology and microbiology

Enzyme , proenzyme; compositions thereof; process for...

Enzyme inactivation by chemical treatment

435190, 536 27, 546123, 546215, 546225, 546237, 546239, C12N 999, C07D47102

Patent

active

049506021

ABSTRACT:
The present invention relates to inhibitors of lactate dehydrogenase that can cross the blood brain barrier and there is described herein the preparation of several analogues of nicotinamide-adenine-dinucleotide (NAD.sup.+) pyruvate adduct, of which 3(-4-(reduced 3-pyridine aldehyde-adenine dinucleotide))-pyruvate (RAP) and similar compounds appear to have a very high affinity for lactate dehydrogenase; one of which (RAP) was shown to strongly inhibit lactate production in rat brain extracts.

REFERENCES:
Lappi et al., Biochemistry, 19: 3841-3845 (1980).
Kaplan et al., J. Biol. Chem., 221: 823-844 (1956).
Anderson et al., J. Biol. Chem., 234: 1219-1232 (1959).
Anderson, "Analogs of Pyridine Nucleotide Coenzymes", in The Pyridine Nucleotide Coenzymes: Academic Press, Inc., N.Y. 1982 pp. 91-131.
Burgner et al., Biochemistry, 17: 1654-1661 (1978).
Everse et al., Organic Chemistry, 1: 207-233 (1971).
Burgner, Biochemistry, 23: 3636-3648 (1984).
Cooper et al., J. Neurochem., 48: 1925-1933 (1987).

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