PubMed Health⌕ Search

Biomedical subjects

N Aman

Publications and source records attributed to N Aman.

4 recordsLinked to original sources
PubMed1994

Conjugates of COL-1 monoclonal antibody and beta-D-galactosidase can specifically kill tumor cells by generation of 5-fluorouridine from the prodrug beta-D-galactosyl-5-fluorouridine.

5'-O-beta-D-galactosyl-5-fluorouridine is a prodrug that can be converted by the enzyme beta-D-galactosidase to the potent antineoplastic drug 5-fluorouridine. The prodrug is more than 100x less toxic than the drug to bone marrow cells in Balb/c mice. The ratio of the IC50 of the prodrug to that of the drug determined on a variety of tumor cell lines in vitro ranged from 500:1-1000:1. An antibody-enzyme conjugate (AEC) was synthesized and purified. Maleimide-substituted COL-1 anti-CEA monoclonal antibody was linked to free thiol groups of beta-D-galactosidase. The conjugate was purified by size exclusion and ion exchange chromatography. It retained full immunoreactivity and enzyme activity. After binding to antigen-positive tumor cells, the conjugate was able to activate the prodrug and specifically kill the cells. We are continuing to investigate this model for its potential use in antibody-directed enzyme prodrug therapy (ADEPT).

Adenocarcinoma↗
PubMed1983

Genetic correlations between six- and seven-week-old broilers.

The genetic relationship between carcass traits in broiler chickens at 6 and 7 weeks of age was determined. Two-hundred and sixteen male broilers from 42 sires and 108 dams with 2 full sibs/dam were slaughtered at 41 and 48 days of age. One offspring per dam was slaughtered at each age. Means of 41-day-old birds are presented first and 48-day-old birds second: live weights 1435, 1872 g; carcass weights 877, 1200 g; abdominal fat weights 23.4, 41.7 g; percent abdominal fat/live weight 2.04, 2.22; percent abdominal fat/carcass weight 3.30, 3.47. Genetic correlations between weeks were: .58 (live weight), .66 (carcass weight), .48 (abdominal fat), .45 (% abdominal fat/live weight), and .42 (% abdominal fat/carcass weight). Records obtained on 6-week-old full sibs might be useful in a selection program to improve traits in 7-week-old birds.

Adipose Tissue↗
PubMedDate not supplied

Aspects of antibody-catalyzed primary amide hydrolysis.

Because there are many known C-terminally amidated peptides of biological importance, there is great potential in medicine and organic synthesis for antibodies that catalyze primary amide bond hydrolysis or formation. We characterized a catalytic antibody, 13D11, raised to a phosphinate hapten, that hydrolyzed the primary amide of a dansyl-alkylated derivative of (R)-phenylalaninamide (DNS-(R)F-NH2). At pH 9.0, 13D11 hydrolyzed DNS-(R)F-NH2 with a kcat of 1.65 x 10(-7) s-1 (kcat/kuncat = 132) and a Km of 432 microM, and was stereospecifically hapten-inhibited (Ki = 14.0 microM). Control experiments indicated that the catalytic activity was not the result of a contaminating protease. In accordance with the hapten being a transition-state analog of base hydrolysis, the rate of DNS-(R)F-NH2 hydrolysis increased with hydroxide concentration to an optimum pH of 9.5. Above pH 9.5, activity declined rapidly suggesting the antibody was inactivated during the long incubation period. This work demonstrates the feasibility of generating catalytic antibodies to hydrolyze unactivated amide bonds without cofactor assistance.

Amides↗