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Biomedical subjects

C J Welch

Publications and source records attributed to C J Welch.

23 records · Page 2Linked to original sources

Pyridyl groups for protection of the imide functions of uridine and guanosine. Exploration of their displacement reactions for site-specific modifications of uracil and guanine bases.

For the protection of the O-4 function of uridine and the O-6 of guanosine, 2-, 3- and 4-hydroxypyridines, 2-pyridinethiol, 6-methyl-2-hydroxy- and 6-methyl-3-hydroxypyridines have been employed. These substituted pyridines gave pyridyl-N-and/or pyridyl-O-substituted derivatives, depending both upon the position of the hydroxyl and methyl groups in the pyridine ring, at the C-4 and the C-6 of the uracil and guanine residues, respectively. These groups were found to be good leaving groups for nucleophilic substitution reactions by amines, thiolates and oximate. If needed, the rate of these substitution reactions could be conveniently increased by almost 1000-fold by conversion of the pyridyl moiety to its methiodide.

Chemical Phenomena↗

Synthesis of an mRNA fragment of alanyl-tRNA synthetase gene in Escherichia coli using the 6-methyl-3-pyridyl group for protection of the imide functions of uridine and guanosine.

The synthesis of 5'-GpGpUpGpU-3' is reported to demonstrate the synthetic use of the 6-methyl-3-pyridyl group for the protection of the O-4 and O-6 imide functions of uridine and guanosine, respectively. The 2'- and 5'-hydroxyl functions of the key intermediates were protected with two acid-labile groups: 3-methoxy-1,5-dicarbomethoxypentane-3-yl (MDMP) and 9-(4-octadecyloxyphenyl)xanthen-9-yl (C18Px), respectively. The internucleotide phosphotriesters were protected with 2-chlorophenyl and the 9-fluorenylmethyl group was employed for 3'-terminal phosphate protection.

Alanine-tRNA Ligase↗

Extended length heterobifunctional coupling agents for protein conjugations.

A series of extended length heterobifunctional coupling agents is described. The successive aminocaproic acid homologation of succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate, a known 9-atom long maleimide active ester linker, yielded 16-, 23-, and 30-atom long maleimide active ester homologues. The performance study of these coupling agents in automated microparticle enzyme immunoassays showed that, in the alpha fetoprotein assay, in which the linkers were employed in the construction of the alkaline phosphatase-antibody conjugates, the signal increased 64% when the length of the linker was incremented from 9 atoms to 23 atoms and 82% for the 30-atom long linker as compared with the 9-atom homologue. Similar improvements were observed in the performance of carbohydrate antigen, marker of ovarian cancer (CA-125), immunoassay where the linkers were used for conjugation of the capture antibody anti-CA-125 to the microparticle. Thus, a 300% signal improvement resulted when a 30-atom linker was used instead of the 9-atom homologue. The observed differences in the performance of the conjugates are interpreted as resulting from improved antibody binding and lowering of the steric hindrance of the complementarity-determined region of the antibody when longer coupling agents were used.

Alkaline Phosphatase↗