PMID: 38003Jun 1, 1979

Analogs of L-aspartic acid in chemotherapy for cancer

Cancer Treatment Reports
H N Jayaram, D A Cooney

Abstract

The interaction of analogs of L-aspartic acid with adenylosuccinic acid synthetase, L-asparagine synthetase, and L-aspartic acid transcarbamylase is discussed. Each of these enzymes is of critical importance in the economy of certain types of tumor cells. L-Alanosine, a new antitumor antibiotic, is shown to be accepted as a substrate by the enzymes of de novo purine biosynthesis which ordinarily use L-aspartic acid as a substrate; as a consequence of this interaction, an anabolite is thought to be produced which impairs the formation of adenine nucleotides by inhibiting adenylosuccinate synthetase, leading to an interruption in DNA synthesis. Homoserine-beta-adenylate, guanidinosuccinic acid, and PA2LA [3-(phosphonacetylamido)-L-alanine] are shown to be inhibitors of L-asparagine synthetase from murine lymphoblasts; each of these analogs of L-aspartic acid exhibits novel structural properties which can be used by synthetic chemists in the design of molecules with an even greater ability to block the biosynthesis of L-asparagine. Certain aspects of the mechanism of action of PALA (N-phosphonacetyl-L-aspartic acid) were examined. This agent, which is a potent inhibitor of mammalian L-aspartic acid transcarbamylase, is capable of ...Continue Reading

Related Concepts

Tumor Cells, Uncertain Whether Benign or Malignant
Guanidinosuccinic acid
Asparagine
Antineoplastic Agents
Enzymes, antithrombotic
Aspartic Acid, Magnesium-Potassium (2:1:2) Salt
Murine
Lymphoblast Count
Analog
Asparagine Synthetase B

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