Site specificity of the inhibitory effect of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simples virus type 1 immediate early mRNA 4

M. Kulka; C. C. Smith; L. Aurelian; R. Fishelevich; K. Meade; P. Miller; P. O.P. Ts'o

doi:10.1073/pnas.86.18.6868

Site specificity of the inhibitory effect of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simples virus type 1 immediate early mRNA 4

M. Kulka, C. C. Smith, L. Aurelian, R. Fishelevich, K. Meade, P. Miller, P. O.P. Ts'o

Research output: Contribution to journal › Article › peer-review

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Abstract

Oligo(nucleoside methylphosphonate)s complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5 caused specific inhibition of herpes simplex virus type 1 growth. The dodecamer d(TpTCCTCCTGCGG)(deoxynucleoside methylphosphonate residues in italic) caused 50% and 98% decreases in herpes simplex virus type 1 titers at concentrations of 15 μM and 100 μM, respectively. d(TpTCCTCCTGCGG) inhibited viral but not cellular protein synthesis and decreased splicing of immediate early pre-mRNAs 4 and 5. Inhibition was highly sequence specific. A psoralen derivative of d(TpTCCTCCTGCGG) that can covalently bind to complementary sequences after exposure to 365-nm irradiation caused 90-98% inhibition of virus growth in cells treated with oligomer (5 μM) and irradiated at 1-3 hr postinfection. The data suggest that oligo(nucleoside methylphosphonate)s of appropriate sequence and derivatization may be effective as antiviral agents.

Original language	English (US)
Pages (from-to)	6868-6872
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	86
Issue number	18
DOIs	https://doi.org/10.1073/pnas.86.18.6868
State	Published - 1989
Externally published	Yes

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Kulka, M., Smith, C. C., Aurelian, L., Fishelevich, R., Meade, K., Miller, P., & Ts'o, P. O. P. (1989). Site specificity of the inhibitory effect of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simples virus type 1 immediate early mRNA 4. Proceedings of the National Academy of Sciences of the United States of America, 86(18), 6868-6872. https://doi.org/10.1073/pnas.86.18.6868

Site specificity of the inhibitory effect of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simples virus type 1 immediate early mRNA 4. / Kulka, M.; Smith, C. C.; Aurelian, L. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 18, 1989, p. 6868-6872.

Research output: Contribution to journal › Article › peer-review

Kulka, M, Smith, CC, Aurelian, L, Fishelevich, R, Meade, K, Miller, P & Ts'o, POP 1989, 'Site specificity of the inhibitory effect of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simples virus type 1 immediate early mRNA 4', Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 18, pp. 6868-6872. https://doi.org/10.1073/pnas.86.18.6868

Kulka M, Smith CC, Aurelian L, Fishelevich R, Meade K, Miller P et al. Site specificity of the inhibitory effect of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simples virus type 1 immediate early mRNA 4. Proceedings of the National Academy of Sciences of the United States of America. 1989;86(18):6868-6872. doi: 10.1073/pnas.86.18.6868

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abstract = "Oligo(nucleoside methylphosphonate)s complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5 caused specific inhibition of herpes simplex virus type 1 growth. The dodecamer d(TpTCCTCCTGCGG)(deoxynucleoside methylphosphonate residues in italic) caused 50% and 98% decreases in herpes simplex virus type 1 titers at concentrations of 15 μM and 100 μM, respectively. d(TpTCCTCCTGCGG) inhibited viral but not cellular protein synthesis and decreased splicing of immediate early pre-mRNAs 4 and 5. Inhibition was highly sequence specific. A psoralen derivative of d(TpTCCTCCTGCGG) that can covalently bind to complementary sequences after exposure to 365-nm irradiation caused 90-98% inhibition of virus growth in cells treated with oligomer (5 μM) and irradiated at 1-3 hr postinfection. The data suggest that oligo(nucleoside methylphosphonate)s of appropriate sequence and derivatization may be effective as antiviral agents.",

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AU - Miller, P.

AU - Ts'o, P. O.P.

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N2 - Oligo(nucleoside methylphosphonate)s complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5 caused specific inhibition of herpes simplex virus type 1 growth. The dodecamer d(TpTCCTCCTGCGG)(deoxynucleoside methylphosphonate residues in italic) caused 50% and 98% decreases in herpes simplex virus type 1 titers at concentrations of 15 μM and 100 μM, respectively. d(TpTCCTCCTGCGG) inhibited viral but not cellular protein synthesis and decreased splicing of immediate early pre-mRNAs 4 and 5. Inhibition was highly sequence specific. A psoralen derivative of d(TpTCCTCCTGCGG) that can covalently bind to complementary sequences after exposure to 365-nm irradiation caused 90-98% inhibition of virus growth in cells treated with oligomer (5 μM) and irradiated at 1-3 hr postinfection. The data suggest that oligo(nucleoside methylphosphonate)s of appropriate sequence and derivatization may be effective as antiviral agents.

AB - Oligo(nucleoside methylphosphonate)s complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5 caused specific inhibition of herpes simplex virus type 1 growth. The dodecamer d(TpTCCTCCTGCGG)(deoxynucleoside methylphosphonate residues in italic) caused 50% and 98% decreases in herpes simplex virus type 1 titers at concentrations of 15 μM and 100 μM, respectively. d(TpTCCTCCTGCGG) inhibited viral but not cellular protein synthesis and decreased splicing of immediate early pre-mRNAs 4 and 5. Inhibition was highly sequence specific. A psoralen derivative of d(TpTCCTCCTGCGG) that can covalently bind to complementary sequences after exposure to 365-nm irradiation caused 90-98% inhibition of virus growth in cells treated with oligomer (5 μM) and irradiated at 1-3 hr postinfection. The data suggest that oligo(nucleoside methylphosphonate)s of appropriate sequence and derivatization may be effective as antiviral agents.

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Site specificity of the inhibitory effect of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simples virus type 1 immediate early mRNA 4

Abstract

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