9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP): A novel agent with anti-human immunodeficiency virus activity in vitro and potent anti-moloney murine sarcoma virus activity in vivo

1989 ◽  
Vol 8 (12) ◽  
pp. 1043-1047 ◽  
Author(s):  
L. Naesens ◽  
J. Balzarini ◽  
I. Rosenberg ◽  
A. Holý ◽  
E. Clercq
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Activity ◽  
Immunodeficiency Virus ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Moloney Murine Sarcoma Virus ◽  
Murine Sarcoma ◽  
Novel Agent

scholarly journals Antiretrovirus Activity of a Novel Class of Acyclic Pyrimidine Nucleoside Phosphonates

2002 ◽  
Vol 46 (7) ◽  
pp. 2185-2193 ◽  
Author(s):  
J. Balzarini ◽  
C. Pannecouque ◽  
E. De Clercq ◽  
S. Aquaro ◽  
C.-F. Perno ◽  
...  
Keyword(s):  
Pyrimidine Nucleotide ◽  
Immunodeficiency Virus ◽  
Murine Sarcoma Virus ◽  
Acyclic Nucleoside Phosphonates ◽  
Sarcoma Virus ◽  
Acyclic Nucleoside ◽  
Murine Sarcoma ◽  
Antiretroviral Activity

ABSTRACT A novel class of acyclic nucleoside phosphonates has been discovered in which the base consists of a pyrimidine preferably containing an amino group at C-2 and C-4 and a 2-(phosphonomethoxy)ethoxy (PMEO) or a 2-(phosphonomethoxy)propoxy (PMPO) group at C-6. The 6-PMEO 2,4-diaminopyrimidine (compound 1) and 6-PMPO 2,4-diaminopyrimidine (compound 11) derivatives showed potent activity against human immunodeficiency virus (HIV) in the laboratory (i.e., CEM and MT-4 cells) and in primary (i.e., peripheral blood lymphocyte and monocyte/macrophage) cell cultures and pronounced activity against Moloney murine sarcoma virus in newborn NMRI mice. Their in vitro and in vivo antiretroviral activity was comparable to that of reference compounds 9-[(2-phosphonomethoxy)ethyl]adenine (adefovir) and (R)-9-[(2-phosphonomethoxy)-propyl]adenine (tenofovir), and the enantiospecificity of (R)- and (S)-PMPO pyrimidine derivatives as regards their antiretroviral activity was identical to that of the classical (R)- and (S)-9-(2-phosphonomethoxy)propyl purine derivatives. The prototype PMEO and PMPO pyrimidine analogues were relatively nontoxic in cell culture and did not markedly interfere with host cell macromolecular (i.e., DNA, RNA, or protein) synthesis. Compounds 1 and 11 should be considered attractive novel pyrimidine nucleotide phosphonate analogues to be further pursued for their potential as antiretroviral agents in the clinical setting.

In Vivo and In Vitro Studies on the Morphogenesis of Tumors Induced by Murine Sarcoma Virus (Harvey) 2

1973 ◽  
Vol 51 (5) ◽  
pp. 1541-1549 ◽  
Author(s):  
W. R. Thomas ◽  
E. J. Aw ◽  
J. M. Papadimitriou ◽  
P. J. Simons
Keyword(s):  
In Vitro Studies ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Murine Sarcoma

scholarly journals Decreased susceptibility to calpains of v-FosFBR but not of v-FosFBJ or v-JunASV17 retroviral proteins compared with their cellular counterparts

1997 ◽  
Vol 323 (3) ◽  
pp. 685-692 ◽  
Author(s):  
Ann-Muriel STEFF ◽  
Serge CARILLO ◽  
Magali PARIAT ◽  
Marc PIECHACZYK
Keyword(s):  
Cysteine Proteases ◽  
Calcium Dependent ◽  
Peptide Motifs ◽  
Interesting Possibility ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Infected Cells ◽  
Murine Sarcoma

The c-Fos and c-Jun transcription factors are rapidly turned over in vivo. One of the multiple pathways responsible for their breakdown is probably initiated by calpains, which are cytoplasmic calcium-dependent cysteine proteases. The c-fos gene has been transduced by two murine oncogenic retroviruses called Finkel-Biskis-Jenkins murine sarcoma virus (FBJ-MSV) and Finkel-Biskis-Reilly murine sarcoma virus (FBR-MSV); c-jun has been transduced by the chicken avian sarcoma virus 17 (ASV17) retrovirus. Using an in vitro degradation assay, we show that the mutated v-FosFBR, but not v-FosFBJ or v-JunASV17, is resistant to calpains. This property raises the interesting possibility that decreased sensitivity to calpains might contribute to the tumorigenic potential of FBR-MSV by allowing greater accumulation of the protein that it encodes in infected cells. It has also been demonstrated that resistance to cleavage by calpains does not result from mutations that have accumulated in the Fos moiety of the viral protein but rather from the addition of atypical peptide motifs at its both ends. This observation raises the interesting possibility that homologous regions in viral and cellular Fos either display slightly different conformations or are differentially accessible to interacting proteins.

scholarly journals In vitro differentiation of rhabdomyosarcomas induced by nickel or by Moloney murine sarcoma virus

1991 ◽  
Vol 63 (5) ◽  
pp. 736-742 ◽  
Author(s):  
P Nanni ◽  
G Azzarello ◽  
L Tessarollo ◽  
C De Giovanni ◽  
P-L Lollini ◽  
...  
Keyword(s):  
In Vitro Differentiation ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Moloney Murine Sarcoma Virus ◽  
Murine Sarcoma

scholarly journals Moloney Murine Sarcoma Virus Genomic RNAs Dimerize via a Two-Step Process: a Concentration-Dependent Kissing-Loop Interaction Is Driven by Initial Contact between Consecutive Guanines

1999 ◽  
Vol 73 (9) ◽  
pp. 7255-7261 ◽  
Author(s):  
Hinh Ly ◽  
Donald P. Nierlich ◽  
John C. Olsen ◽  
Andrew H. Kaplan
Keyword(s):  
Viral Replication ◽  
Genomic Rnas ◽  
Rna Dimerization ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Moloney Murine Sarcoma Virus ◽  
Murine Sarcoma ◽  
Palindromic Sequences ◽  
Kissing Loop

ABSTRACT Retroviruses contain two plus-strand genomic RNAs, which are stably but noncovalently joined in their 5′ regions by a dimer linkage structure (DLS). Two models have been put forward to explain the mechanisms by which the RNAs dimerize; each model emphasizes the role of specific molecular determinants. The kissing-loop model implicates interactions between palindromic sequences in the DLS region. The second model proposes that purine-rich stretches in the region form purine quartet structures. Here, we present an examination of the in vitro dimerization of Moloney murine sarcoma virus (MuSV) RNA in the context of these two models. Dimers were found to form spontaneously in a temperature-, time-, concentration-, and salt-dependent manner. In contrast to earlier reports, we found that deletion of neither the palindrome nor the consensus purine motifs (PuGGAPuA) affected the level of dimer formation at low concentrations of RNA. Rather, different purine-rich sequences, i.e., consecutive stretches of guanines, were found to enhance both in vitro RNA dimerization and in vivo viral replication. Biochemical evidence further suggests that these guanine-rich (G-rich) stretches form guanine quartet structures. We also found that the palindromic sequences could support dimerization at significantly higher RNA concentrations. In addition, the G-rich stretches were as important as the palindromic sequence for maintaining efficient viral replication. Overall, our data support a model that entails contributions from both of the previously proposed mechanisms of retroviral RNA dimerization.

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