Abstract

The principal objective of the proposal is to develop chemotherapeutic approaches for metastatic tumors based on recently acquired knowledge relating cell surface carbo-hydrates to detachment and implantation of potentially metastatic cells. Inhibitors of sialic acid biosynthesis and its transfer may prevent implantation of metastatic tumors as well as affecting the immunogenicity of the cancer cells. We shall by synthesizing analogues of D-glucosamine, D-mannosamine, NANA, CMP-NANA and D-galactose potentially affecting the anabolic pathways of glycoconjugate biosynthesis. Their effects on hexokinase, CMP-NANA synthetase and CMP-NANA transferase will be determine. All carbohydrate analogs will be tested in metastatic tumors and their effects on immunogenicity will be evaluated. Other test systems have been designed to evaluate their effects on cell surface properties, such as cell surface sialic acid, lectin agglutination and cell social behavior. Combination chemotherapy studies of biologically, active sugar analogs with adriamycin, tunicamycin and local anesthetis are proposed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA008793-17
Application #
3163330
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1978-05-01
Project End
1986-10-30
Budget Start
1985-05-01
Budget End
1986-10-30
Support Year
17
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263

  Publications

Angelino, N J; Bernacki, R J; Sharma, M et al. (1995) Versatile intermediates in the selective modification of the amino function of 2-amino-2-deoxy-D-mannopyranose and the 3-position of 2-acetamido-2-deoxy-D-mannose: potential membrane modifiers in neoplastic control. Carbohydr Res 276:99-115
Sharma, M; Bernacki, R J; Hillman, M J et al. (1993) Fluorinated carbohydrates as potential plasma membrane modifiers. Synthesis of 3-deoxy-3-fluoro derivatives of 2-acetamido-2-deoxy-D-hexopyranoses. Carbohydr Res 240:85-93
Petrie 3rd, C R; Sharma, M; Simmons, O D et al. (1989) Synthesis of analogs of N-acetylneuraminic acid and their effect on CMP-sialate synthase. Carbohydr Res 186:326-34
Lee, H H; Hodgson, P G; Bernacki, R J et al. (1988) Analogs of cell surface carbohydrates. Synthesis of D-galactose derivatives having an ethynyl, vinyl or epoxy residue at C-5. Carbohydr Res 176:59-72
Sharma, M; Petrie 3rd, C R; Korytnyk, W (1988) General methods for modification of sialic acid at C-9. Synthesis of N-acetyl-9-deoxy-9-fluoroneuraminic acid. Carbohydr Res 175:25-34
Jain, R K; Abbas, S A; Matta, K L (1987) Selective phosphorylation of the primary hydroxyl groups of methyl 2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside. Carbohydr Res 161:318-23
Dubey, R; Jain, R K; Abbas, S A et al. (1987) Synthesis of methyl 3-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 3-O-alpha-D-talopyranosyl-alpha-D-talopyranoside. Carbohydr Res 165:189-96
Jain, R K; Dubey, R; Abbas, S A et al. (1987) Synthesis of methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside. Carbohydr Res 161:31-7
Sharma, M; Potti, G G; Simmons, O D et al. (1987) Fluorinated carbohydrates as potential plasma membrane modifiers and inhibitors. Synthesis of 2-acetamido-2,6-dideoxy-6-fluoro-D-galactose. Carbohydr Res 162:41-51
Chowdhary, M S; Jain, R K; Rana, S S et al. (1986) A synthesis of methyl 3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside and related disaccharides. Carbohydr Res 152:323-8

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