Publication

Structure-activity studies of novel D-Ser8-cyclosporine A derivatives as potential anti-HIV drugs

2002
Conference Papers

Abstract

A symposium report. Since the discovery of the immunosuppressive activity of cyclosporine A (CsA), considerable work has been devoted to the chem. synthesis of potent analogs. More recently, the finding of potential anti-HIV I activity of CsA raised interest for the design of CsA-derived compds. devoid of immunosuppressive activity. With this objective, the highly immunosuppressive CsA analog DSer8CsA was taken as a versatile candidate for modulating the binding mode to its receptors cyclophilin A (CypA) and calcineurin A (CnA). To this end, the functional group at position 8 of 1 is used for the chemoselective transformation to substituted pseudoproline systems and to dimers disposing variable linkers. Direct-transformation of a serine or threonine to a pseudoproline (PPro) has been shown to be a valuable method to tune the activity of bioactive compds.. Here the authors applied this strategy to DSer8CsA using various monosubstituted dimethoxyacetals in the presence of pyridium p-toluenesulfonate. In vitro activities of cyclosporin derivs. were evaluated applying the IL-2 reporter gene assay (measuring immunosuppressive activity) and the binding affinity to CypA (related to the anti-HIV activity). In conclusion, SAR studies of DSer8CsA derivs. applying the PPro concept and dimerization techniques at position 8 reveal differential effects on receptor binding, resulting in compds. of high therapeutical interest. [on SciFinder (R)]

Official source

https://infoscience.epfl.ch/entities/publication/a687301b-2dec-4fbd-a28c-18175d2d4fb6

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2002
Conference Papers

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/a687301b-2dec-4fbd-a28c-18175d2d4fb6

About this result

Related concepts (32)

Management of HIV/AIDS

The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death.

HIV/AIDS

Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual may not notice any symptoms, or may experience a brief period of influenza-like illness. Typically, this is followed by a prolonged incubation period with no symptoms.

Ligand (biochemistry)

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ligare, which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix.