SYNTHESIS OF MONOMERIC CARCINOGEN-DNA ADDUCTS

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: N/A
Agency Tracking Number: 11139
Amount: $50,000.00
Phase: Phase I
Program: SBIR
Awards Year: 1989
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
4636 E Elwood St #6, Phoenix, AZ, 85040
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 () -
Business Contact
Phone: () -
Research Institution
N/A
Abstract
RESEARCH ON MECHANISMS IN CHEMICAL CARCINOGENESIS OFTEN REQUIRES AUTHENTIC MONOMERIC CARCINOGEN-DNA ADDUCTS. FEW ADDUCTS ARE COMMERCIALLY AVAILABLE, AND INDIVIDUALS OFTEN OBTAIN SUBMILLIGRAM LEVELS OF ADDUCTS FROM CARCINOGEN-TREATED DNA; THIS MAY BE INSUFFICIENT FOR THEIR NEEDS. THE OBJECTIVE OF THIS PROJECT IS TO DETERMINE THE FEASIBILITY OF DEVELOPING GENERIC APPROACHES TO GRAM-SCALE SYNTHESIS OF CARCINOGEN-DNA ADDUCTS THAT MAY BE USED IN MODERN MOLECULAR TOXICOLOGY STUDIES AS POSTLABELING OR CHROMATOGRAPHY STANDARDS, IN DEVELOPING IMMUNOASSAYS, OR FOR INCORPORATION INTO OLIGONUCLEOTIDES. THIS PROJECT WILL SPECIFICALLY ADDRESS PREPARATION OF 3'-MONOPHOSPHATES OF MAJOR ADDUCTS OF DG AND DA WITH 7-BROMOMETHYL-12-METHYLBENZANTHRACENE (BMBA) OR BENZO(A)PYRENE DIOLEPOXIDE I (BPDE), AS STANDARDS FOR THE (32)P-POSTLABELING ASSAY. SILYLATION VERSUS ACYLATION WILL BE EVALUATED FOR TRANSIENT PROTECTION OF BPDE AND DEOXYRIBOSE HYDROXYLS; THEIR STABILITY DURING PHOSPHORYLATION AND EASE OF SELECTIVE REMOVAL WILL BE CHECKED. O-SILYLATED OR -ACYLATED AMINES (FROM AMMONIATION OF BPDE OR BMBA) WILL BE CONDENSED WITH THE APPROPRIATE PROTECTED HALOPURINE NUCLEOSIDE TO YIELD FULLY BLOCKED N(2)-DG OR N(6)-DA DERIVATIVES. PHOSPHORYLATION WILL FOLLOW SELECTIVE REMOVAL OF THE 3'-PROTECTING GROUP.

* Information listed above is at the time of submission. *

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