Retroviruses by definition insert their viral genome into the host cell chromosome. Although the key player of retroviral integration is viral integrase, a role for cellular cofactors has been proposed. Lentiviral integrases use the cellular protein LEDGF/p75 to tether the preintegration complex to the chromosome, although the existence of alternative host proteins substituting for the function...

The increasing incidence of resistance to current HIV-1 therapy underscores the need to develop antiretroviral agents with new mechanisms of action. Integrase, one of three viral enzymes essential for HIV-1 replication, presents an important yet unexploited opportunity for drug development. We describe here the identification and characterization of L-870,810, a small-molecule inhibitor of HIV-...

An essential step in the replication of retroviruses is the integration of a DNA copy of the viral genome into the genome of the host cell. Integration involves a series of well defined DNA cleavage and strand-transfer steps that are catalyzed by the virally encoded enzyme integrase (1 —4). The sequence-specific endonucleolytic activity of integrase removes two nucleotides from the 3' end of ea...

OBJECTIVES The Streptomyces phage phiC31 integrase offers a sequence-specific method of transgenesis with a robust long-term gene expression. PhiC31 has been successfully developed in a variety of tissues and organs for purpose of in vivo gene therapy. The objective of the present experiment was to evaluate PhiC31-based site-specific transgenesis system for production of transgenic bovine embry...

Systems for introducing DNA genes-of-interest into mammalian cellular genomes have ranged from the use of different physical techniques to viruses including retroviruses. We have developed a microinjection method for an efficient and permanent integration of a DNA transgene into the cell genome by use of the retrovirus integrase. A 3.0-kb linear DNA fragment containing an internal herpes simple...

Most temperate phages encode an integrase for integration and excision of the prophage. Integrases belong either to the lambda Int family of tyrosine recombinases or to a subgroup of the serine recombinases, the large serine recombinases. Integration by purified serine integrases occurs efficiently in vitro in the presence of their cognate (~50 bp) phage and host attachment sites, attP and attB...

The interaction of molecular iodine with virus DNA nucleotide is studied by ab initio RHF/321G** method. Formation of the nucleoprotein complex of the HIV DNA, molecular iodine and the HIV-1 integrase co-factor is considered to cause the inhibition action of the integrase enzyme. Experimental data on the anti-HIV effect of the molecular iodine complex compounds and the results of calculations s...

Background S/GSK1349572 is a new integrase inhibitor (INI) with in-vitro activity against INI-resistant HIV. Before dosing a large number of subjects in pivotal clinical trials, in-vitro findings were validated in a pilot clinical study (ING112961). At the outset of the study, the degree of susceptibility at which the drug no longer provides benefit was unknown. Planned enrollment for this stud...

Blinatumomab, the bispecific T cell engager, has been demonstrated as the most successful BsAb to date. Throughout the past decade, vector design has great importance for the expression of monoclonal antibody in Chinese hamster ovary (CHO) cells. It has been indicated that expression plasmids based on the elongation factor-1 alpha (EF-1 alpha) gene and DHFR selection marker can be highly effect...

In an attempt to identify potential new agents that are active against HIV-1, a series of novel pyridopyrimidine-5-carbohydrazide derivatives featuring a substituted benzylidene fragment were designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors. The cytotoxicity profiles of these compounds showed no significant toxicity to human cells and they exhibited anti...