Biomedical subjects

G Gosselin

Publications and source records attributed to G Gosselin.

At least 127 records · Page 7Linked to original sources

PubMed1984

Mechanism of inhibition of herpesvirus growth by 2'-5'-linked trimer of 9-beta-D-xylofuranosyladenine.

The 2'-5'-linked trimer of 9-beta-D-xylofuranosyladenine (XyloA)3 is an extremely potent inhibitor of growth of herpes simplex viruses 1 and 2. Evidence is presented that in spite of its increased stability in cell-free extracts (D.A. Eppstein, Y.V. Marsh, B.B. Schryver, M.A. Larsen, J.W. Barnett, J.P.H. Verheyden, and E.J. Prisbe, J. Biol. Chem. 257, 13390-13397, 1982), intact (XyloA)3 was not detected in Vero cells, but instead was rapidly degraded in the medium to monomeric 9-beta-D-xylofuranosyladenine (XyloA). The XyloA thus formed was rapidly taken up by cells, phosphorylated to its triphosphate, and produced inhibition of RNA synthesis. The observed inhibition of DNA synthesis (D.A. Eppstein, Y.V. Marsh, B.B. Schryver, M.A. Larsen, J.W. Barnett, J.P.H. Verheyden, and E.J. Prisbe, J. Biol. Chem. 257, 13390-13397, 1982) and herpesvirus growth by (XyloA)3 (D.A. Eppstein, J.W. Barnett, Y.V. Marsh, G. Gosselin, and J.L. Imbach, Nature (London) 302, 723, 724, 1983) is most likely the result of inhibition of RNA synthesis by its degradation product XyloA.

Acyclovir↗

PubMed1983

Conformational characteristics of the trinucleoside diphosphate xyloA2'-5'xyloA2'-5'xyloA. A nuclear magnetic resonance and CD study.

In this paper the conformational analysis of the 2'-5' linked xylotrinucleotide xA2'-5'xA2'-5'xA is reported. The title compound is an analogue of A2'-5'A2'-5'A, which compound was shown to display inhibitive effects on protein synthesis. The complete 1H-NMR assignment of the high field spectral region of the xylose trimer is given. Modes of base-base stacking are extracted from coupling constant data at various temperatures. Circular dichroic (CD) spectra confirm the presence of stacked states at low temperature. Xylonucleosides are known to prefer the N-type sugar conformation. However, in the present trimer the S-type conformer is suggested to partake in stacked conformations. Two types of stacking in the two constituent dimer fragments of the trimer are proposed to rationalize the NMR data: xA(1)N-xA(2)S and xA(2)N-xA(3)S.

Circular Dichroism↗

PubMed1983

Xyloadenosine analogue of (A2'p)2A inhibits replication of herpes simplex viruses 1 and 2.

Molecules of the structure ppp(A2'p)2A containing a 2' leads to 5' phosphodiester bond, commonly abbreviated as 2-5A, are synthesized in interferon-treated virally-infected cells and have been implicated in several systems as contributing to interferon's antiviral activity. The 2-5A binds to and subsequently activates an endogenous endonuclease, ultimately resulting in degradation of RNA. We have been interested in the use of 2-5A analogues to achieve antiviral activity without the use of interferon. For this approach to be successful, analogues must be synthesized with an increased stability (native 2-5A is rapidly degraded by cellular phosphodiesterases) and with increased ability to enter intact cells. Removal of the highly-negative charged 5' terminal phosphates from ppp(A2'p)2A results in formation of the 'core' species, (A2'p)2A, which should be able to penetrate intact cells more readily. While Kimchi et al. have shown that 2-5A core has an antimitogenic effect in mouse spleen lymphocytes and 3T3 fibroblasts, Williams and Kerr have reported lack of antiviral activity against Semliki Forest virus or encephalomyocarditis virus by exogenously-administered 2-5A core. We have previously determined that (xyloA2'p)2xyloA (abbreviated as xylo 2-5A core), the xyloadenosine analogue of the 5'-terminally dephosphorylated 2-5A core, is over 100 times more stable than the parent 2-5A core species. We now report that this xylo 2-5A core inhibits replication of herpes simplex viruses 1 and 2 in vitro, with greater than 100 times the activity of the parent 2-5A core. The mechanism of antiviral action of the 2-5A core analogue appears to involve a pathway different from that activated by the parent 5' triphosphorylated 2-5A species.

Adenine Nucleotides↗

PubMed1982

Nucleoside synthons and unusual oligonucleotides.

The syntheses of oligonucleotides are generally performed using commercial nucleoside synthons. In certain cases, however, when rare nucleosides containing modified sugar moieties or aglycones are desired it is necessary to synthesize the individual nucleoside precursors. We now report, herein, data on the preparation of two different series of nucleoside synthons. The first concerns the preparation of some 2'-O-methylnucleosides and the second involves synthesis of xylofuranosyladenine analogs and the eventual preparation of 2',5'-(xyloA)3, a potential interferon mediator.

Methods↗

PubMed1976

Design and evaluation of head unit for wheelchair control by quadriplegic patients.

A control unit was designed to allow persons who have lost hand and arm function to control the speed, steering, reversal and on-off switching of an electric wheelchair by means of backward movement and rotation of the head. When possible, shoulder movement was used to control both reversal and on-off switching. Clinical evaluation in 10 patients with quadriplegia and 2 with severe neuromuscular disease showed that the unit neither interfered with nor restrained the patients' residual body movements, permitted use of natural head movements for smooth and fast control of the wheelchair, and was well accepted by and integrated into the life of the patients.

Accident Prevention↗

PubMed1976