Of a series of nucleoside analogues synthesised, 9-(2-hydroxyethoxymethyl) guanine was found to have marked antiviral activity in animal models of herpes virus infections, associated with very low toxicity.
Research on antimetabolites of nucleic acid purines led to drugs for the treatment of acute leukemia (6-mercaptopurine and thioguanine), gout and hyperuricemia (allopurinol), and herpesvirus infections (acyclovir), and for the prevention of organ transplant rejection (azathioprine).
A guanine derivative with an acyclic side chain, 2-hydroxyethoxymethyl, at position 9 has potent antiviral activity [dose for 50% inhibition (ED50) = 0.1 ,uM] against herpes simplex virus type 1. This acyclic nucleoside analog, termed acycloguanosine, is converted to a monophosphate by a virusspecified pyrimidine deoxynucleoside (thymidine) kinase and is subsequently converted to acycloguanosine di-and triphosphates. In the uninfected host cell (Vero) these phosphorylations of acycloguanosine occur to a very limited extent. Acycloguanosine triphosphate inhibits herpes simplex virus DNA polymerase (DNA nucleotidyltransferase) 10-30 times more effectively than cellular (HeLa S3) DNA polymerase. These factors contribute to the drug's selectivity; inhibition of growth of the host cell requires a 3000-fold greater concentration of drug than does the inhibition of viral multiplication. There is, moreover, the strong possibility of chain termination of the viral DNA by incorporation of acycloguanosine.The identity of the kinase that phosphorylates acycloguanosine was determined after separation of the cellular and virus-specified thymidine kinase activities by affinity chromatography, by reversal studies with thymidine, and by the lack of monophosphate formation in a temperature-sensitive, thymidine kinase-deficient mutant of the KOS strain of herpes simplex virus type 1 (tsAl).
Nachhaltigkeit ist zugleich historisches Kulturgut und moderne Antwort auf die aktuelle globale Krisensituation im Kontext des Klimawandels. Insbesondere im Bauwesen ist der strategische Ansatz der Nachhaltigkeit in den letzten Jahren durch die Entwicklung und Implementierung von Nachhaltigkeitszertifizierungssystemen fest verankert worden. Derzeit weist die Bau‐ und Immobilienwirtschaft vor allem in den Bereichen der Diversifikation entwickelter Bewertungs‐ und Optimierungswerkzeuge und der Ausbildung eines praxistauglichen rechtlichen Rahmens für die beteiligten Akteure eine wesentliche Dynamik auf.
Beyond Platin – Sustainability trends in the construction and real estate industry. Sustainability is both a cultural asset and a modern answer to the current global crisis of climate change. In the past few years, sustainability has become especially important in the construction industry, anchored by the development and implementation of a number of sustainability certification systems. Today, the construction and real estate industry shows an essential dynamism in areas of diversifying of the developed assessment and optimization tools as well as establishing of a suitable legal framework for the involved players.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.