Biomedical subjects
Publications and source records attributed to G C Chow.
Two brothers with a painful neuropathy as a component of late-onset GM2 gangliosidosis of the Sandhoff type are presented. A dramatic response of the severe dysesthesias to amitriptyline and gabapentin is described. Symptomatic sensory neuropathy may be a component of late-onset GM2 gangliosidosis.
The proteinase encoded by human immunodeficiency virus type 1 (HIV-1) cleaves peptide substrates of sequences derived from processing sites in HIV-1 gag-pol polypeptide. Based on this cleavage, assays that utilize HPLC to measure activity of HIV-1 proteinase are reported herein. In the assay first described, a baseline separation of unlabeled substrate and products is achieved with a run time of 10 min and UV detection. Enzyme concentrations as low as 1 nM, which is the lowest reported for an assay employing underivatized peptide substrate, are attained. Even more powerful, versatile and sensitive, a second method that takes advantage of a peptide substrate labeled at its N-terminus with the fluorescein derivative is described as well. Because of the fluorescein label, this method offers several superior features, including very fast analysis of substrate and product in less than 3 min and fluorescence detection which provides essentially total freedom from interference. Synthesis of fluorescein-labeled peptide substrate is accomplished by solid-phase peptide synthesis.
Dibenz[b,f][1,4]oxazepin-11(10H)-ones (III), pyrido[2,3-b][1,4]benzoxazepin-6(5H)-ones (IV), and pyrido[2,3-b]- [1,5]benzoxazepin-5(6H)-ones (V) were found to inhibit human immunodeficiency virus type 1 reverse transcriptase with IC50 values as low as 19 nM. A-ring substitution has a profound effect on activity, with appropriate substituents at the positions ortho and para to the lactam nitrogen providing dramatically enhanced potency. Substitution in the C-ring is generally neutral or detrimental to activity. Although a C-ring amino substituent at the position meta to the lactam carbonyl is generally beneficial to activity, it has essentially no effect when the A-ring is optimally substituted. Like the dipyridodiazepinone nevirapine, compounds III-V are specific for HIV-1 RT, exhibiting no inhibitory activity against HIV-2 RT or other virial reverse transcriptase enzymes.
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