Chapter title |
Gamma-linked dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8- dideazafolate as antitumour agents.
|
---|---|
Chapter number | 118 |
Book title |
Chemistry and Biology of Pteridines and Folates
|
Published in |
Advances in experimental medicine and biology, January 1993
|
DOI | 10.1007/978-1-4615-2960-6_118 |
Pubmed ID | |
Book ISBNs |
978-1-4613-6287-6, 978-1-4615-2960-6
|
Authors |
Jackman, A L, Bisset, G M, Jodrell, D I, Gibson, W, Kimbell, R, Bavetsias, V, Calvert, A H, Harrap, K R, Stephens, T C, Smith, M N, Jackman, A. L., Bisset, G. M. F., Jodrell, D. I., Gibson, W., Kimbell, R., Bavetsias, V., Calvert, A. H., Harrap, K. R., Stephens, T. C., Smith, M. N., Boyle, F. T. |
Abstract |
Our search for water-soluble quinazoline TS inhibitors that are transported into cells via the RFC, but are not substrates for FPGS, led us to the synthesis of dipeptide analogues of ICI 198583 diglutamate. Although a number of dipeptide analogues were active against isolated TS and L1210 cells in vitro, lack of in vivo stability was a problem. This was circumvented by the synthesis of modified dipeptides where either the alpha-carboxyl of the second amino acid was removed (alpha'-COOH) e.g. -L-glu-GABA or where the second amino acid was the unnatural D-enantiomer e.g.-L-glu-D-glu. Further studies were performed with the -L-glu-D-glu and its 7-CH3, 2'F modified analogue, demonstrating that they use the RFC for cell entry but are not active through polyglutamate formation. The latter compound was tested against experimental tumour models and found to have good activity. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 2 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Professor > Associate Professor | 1 | 50% |
Student > Bachelor | 1 | 50% |
Researcher | 1 | 50% |
Readers by discipline | Count | As % |
---|---|---|
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 50% |
Medicine and Dentistry | 1 | 50% |