Working together to uncover the truth: A molecule-sized diagnostic system combining several recognition elements and four fluorescence-emission channels enabled the identification of a wide range of pharmaceuticals on the basis of distinct photophysical processes. The molecular sensor (see simplified representation; ID = identification) was also used to analyze drug concentrations and combinations in urine samples in a high-throughput manner.

Understanding the structural organization of lipids in the cell and viral membranes is essential for elucidating mechanisms of viral fusion that lead to entry of enveloped viruses into their host cells. The HIV lipidome shows a remarkable enrichment in dihydrosphingomyelin, an unusual sphingolipid formed by a dihydrosphingosine backbone. Here we investigated the ability of dihydrosphingosine to incorporate into the site of membrane fusion mediated by the HIV envelope (Env) protein. Dihydrosphingosine as well as cholesterol, fatty acid, and tocopherol was conjugated to highly conserved, short HIV-1 Env-derived peptides with no antiviral activity otherwise. We showed that dihydrosphingosine exclusively endowed nanomolar antiviral activity to the peptides (IC(50) as low as 120 nM) in HIV-1 infection on TZM-bl cells and on Jurkat T cells, as well as in the cell-cell fusion assay. These sphingopeptides were active against enfuvirtide-resistant and wild-type CXCR4 and CCR5 tropic HIV strains. The anti-HIV activity was determined by both the peptides and their dihydrosphingosine conjugate. Moreover, their mode of action involved accumulation in the cells and viruses and binding to membranes enriched in sphingomyelin and cholesterol. The data suggest that sphingopeptides are recruited to the HIV membrane fusion site and provide a general concept in developing inhibitors of sphingolipid-mediated biological systems.

Ein diagnostisches Molekül, das mehrere Erkennungselemente und vier Fluoreszenzemissionskanäle enthält, ermöglichte die Identifizierung verschiedenster Pharmazeutika auf der Grundlage charakteristischer photophysikalischer Prozesse. Der molekulare Sensor (siehe vereinfachte Darstellung; ID=Identifizierung) wurde auch eingesetzt, um Wirkstoffkonzentrationen in Urinproben im Hochdurchsatz zu analysieren.

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Ein fluoreszierender molekularer Sensor kann die Funktion optischer kreuzreaktiver Sensoranordnungen imitieren. In ihrer Zuschrift auf zeigen D. Margulies et al. die Anordnung einer Reihe nichtspezifischer fluoreszierender Rezeptoren auf einem einzigen Molekül. Das diagnostische Molekül erzeugt eindeutige optische Fingerabdrücke für verschiedene Pharmazeutika und ermöglicht die Analyse von Wirkstoff‐Kombinationen und ‐Konzentrationen in Urinproben im Hochdurchsatz.