Pierre De Somer

(S)-9-(2,3-Dihydroxypropyl)adenine: An Aliphatic Nucleoside Analog with Broad-Spectrum Antiviral Activity

(S)-9-(2,3-Dihydroxypropyl)adenine, a novel nucleoside analog, the sugar moiety of which is replaced by an aliphatic chain, inhibits the replication in vitro of several DNA and RNA viruses, including vaccinia, herpes simplex (types 1 and 2), measles, and vesicular stomatitis. It is also effective in vivo in reducing the mortality rate of mice inoculated intranasally with vesicular stomatitis virus.

Poly(rI) more important than poly(rC) in the interferon induction process by poly(rI)·poly(rC)

Abstract A significantly greater interferon production has been obtained in primary rabbit kidney cell cultures exposed to poly(rI) followed by poly(rC) than in cell cultures exposed to poly(rC) followed by poly(rI). The interferon response in cell cultures exposed to poly(rI) followed by poly(rC) was markedly more resistant to poly- l -lysine and pancreatic ribonuclease treatment than was the interferon response in cell cultures exposed to poly(rC) followed by poly(rI). In addition, poly- l -lysine treatment removed a substantially greater proportion of cell-associated radioactivity from cells exposed to [ 3 H]poly(rC) followed by poly(rI) than from cells exposed to poly(rI) followed by [ 3 H]poly(rC). These findings suggest that the poly(rI) · poly(rC) complex is more tightly and efficiently bound to the cell (surface) when the homopolymers are added in the order poly(rI), poly(rC) than when they are added in the order poly(rC), poly(rI) and that it is more effectively attached to the cell receptor site by its poly(rI) strand rather than by its poly(rC) strand.

Protective effects of anionic detergents on interferons: reversible denaturation.

Abstract Mouse L-cell interferon preparations were normally quite labile to heat, repeated freezing and thawing and chemical manipulations. In the presence of anionic detergents, decyl-, dodecyl- or tetradecylsulfate, the interferons were partially or completely stabilized against all these denaturants, depending on the intactness or disruption of disulfide bonds, respectively. The requirement for disulfide reduction for stabilization of the majority of the activity of interferons in detergents suggests there are two distinct molecular populations of interferons in the preparations.

Anti-complement activity of polynucleotides

Abstract A biologic assay system, based on complement (C′) inhibition, is described to unravel structural differences among polynucleotides. The C′ system appears particularly suitable to distinguish (1) homo- from copoly-ribonucleotides, (2) deoxyribo- from 2′-OH and other 2′-modified polynucleotides, and (3) single homopolynucleotides from double- or triple-stranded complexes. From these studies a number of polynucleotides emerged with potent anti-C′ activities, worthy of further investigation. The most active polymers were (G) n (polyguanylic acid), (dCc1) n [poly(2′-chloro-2′deoxycytidylic acid)] and (dUz) n [poly(2′-azido-2′-deoxyuridylic acid)].

Renaturation of Inactivated Interferons by “Defensive Reversible Denaturation”

Abstract Interferon preparations whose activities had been either partially or completely destroyed by a variety of denaturing conditions could be restored to full activity by converting the inactive conformations to linear random coils and “defending” these linear polypeptides with the anionic detergent, sodium dodecyl sulfate, prior to renaturation. Complete restoration of biological activity of both mouse interferons and human fibroblast interferon required that disulfide bonds be reduced prior to renaturation, but partial reactivation was possible without reduction; these data suggest that both mouse and human fibroblast interferon preparations contain distinct molecular species of interferons.