No abstract

The I70-NMR. chemical shifts of the enriched amino acids glycine, aspartic acid and glutamic acid were measured in aqueous solution as a function of pH. High magnetic fields are necessary to resolve the a,p-and u , y-carboxyl resonances of aspartic acid and glutamic acid, respectively. The chemical shifts of acetic acid were measured for comparative reasons. Ionization constants and titration shifts were obtained by nonlinear least-squares fits to one-proton titration curves. The average excitation energy approximation is discussed in terms of the observed changes in 170-shielding on deprotonation. No intramolecular association between the a-amino group and the a-carboxyl group in the zwitterionic form is required to explain the high-frequency shift of the carboxylate ion. Also no indication of an intramolecular association between the a -amino group and the side-chain carboxyl groups of aspartic acid or glutamic acid was found.

No abstract

The following derivatives of 2'-deoxy-5'-O-1",3",2"-dioxaphosphacyclohex-2" -yluridine 2"-oxide have been synthesised: 5-fluoro (4), 5"-(benzyloxy)-5-methyl (6), 5"-(benzyloxy)-5-fluoro (7), 5"-hydroxy-5-methyl (8), 5-fluoro-5"-hydroxy (9), 5",5"-difluoro-5-methyl (11), and 5,5",5"-trifluoro (12). Compounds 4, 9, and 12 have been evaluated for their inhibitory effects on the growth and metabolism of murine leukemia L1210 cells. Compound 12 was nearly as potent as 2'-deoxy-5-fluorouridine in its inhibitory effect on these cells (ID50 = 0.003 and 0.001 micrograms/mL, respectively). Compounds 4 and 9 were about 300 times less active than 12. None of the compounds was an inhibitor of the cell-free thymidylate synthetase, although their antiproliferative effects were achieved by the inhibition of this enzyme.

The cis and trans isomers of both the enriched carboxy and amide groups of N-acetyl-L-proline can be observed by 170 n.m.r. spectroscopy and are shown in each case to give parallel pH titration curves.