The human neutrophil NADPH oxidase-associated H+ channel acts as a charge compensator for the electrogenic generation of superoxide (O2-.). The expression of the channel activity was found to increase in parallel with that of the stimulatable generation of O2-. in differentiated HL60 cells. HL60 cells induced to differentiate in the presence of succinyl acetone (a inhibitor of heme synthesis) were unable to generate O2-., failed to express p22-phox but retained H+ channel activity. EBV transformed B lymphocyte cell lines from normal and CGD patients lacking expression of either p47-phox or p67-phox all expressed unaltered channel activity; however, the activity was completely absent in the lymphocyte cell line lacking gp91-phox. CHO cells and undifferentiated HL60 cells transfected with gp91-phox cDNA expressed H+ channel activity correlating with the expression of gp91-phox. We therefore conclude that the large subunit of the NADPH oxidase cytochrome b (gp91-phox) is the arachidonate activable H+ channel of human neutrophils.

( I . IX.93) 2'-5' Adenylate trimers 41-44 carrying the (tert-buty1)dimethylsilyl (tbds) group at the 3'-OH position of various sugar moieties were synthesized oiu the phosphoramidite method. The use of the (tert-buty1oxy)carbonyl (boc) and 2-(4-nitrophenyl)ethylsulfonyl (npes) groups for 2'-OH protection in neighbourhood to the 3'49-tbds residue was compared during the synthesis of the target trimers. For other functional positions, the use of the 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) blocking groups were favoured.

59-77, are treated directly with 2-(4-nitrophenyl)ethylsulfonyl chloride forming in all cases a mixture of the 2',3'-di-U-and the two possible 2'-and 3'-0-monosulfonates 107-148 which can be separated into the pure components by chromatographic methods. The npes group is more labile towards DBU cleavage than the corresponding base-protecting 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) groups allowing selective deblocking which is of great synthetic potential.

No abstract

It is shown that the groups (I) (= NPE) and (II) (= NPEOC) are very versatile blocking groups for effectively protecting all functions in nucleosides and nucleotides.