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Aphidicolin

The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform

G E Trantor – 1st expert on this subject based on the ideXlab platform

  • isosteres of the dna polymerase inhibitor Aphidicolin as potential antiviral agents against human herpes viruses
    Journal of Medicinal Chemistry, 1993
    Co-Authors: David L Selwood, J N Champness, J Gillam, D K Hibberd, Karamjit Singh Jandu, D Lowe, M Pether, J Selway, G E Trantor

    Abstract:

    : A variety of isosteres of the DNA polymerase inhibitor Aphidicolin were synthesized as potential antiherpes agents. Modeling studies indicated that the bicyclooctane C, D rings of Aphidicolin could be replaced by an aromatic moiety while maintaining the spatial arrangement of the hydroxyl group equivalent to the essential C18 hydroxyl group of Aphidicolin. Of the racemic isosteres synthesized only 13, the compound with the greatest structural similarity to Aphidicolin, showed any significant antiviral activity in primary assays. An enantioselective synthesis of the compound was carried out and the 4aS isomer 36 was shown to account for the observed antiviral activity noted against herpes simplex virus 1 and human cytomegalovirus.

David L Selwood – 2nd expert on this subject based on the ideXlab platform

  • isosteres of the dna polymerase inhibitor Aphidicolin as potential antiviral agents against human herpes viruses
    Journal of Medicinal Chemistry, 1993
    Co-Authors: David L Selwood, J N Champness, J Gillam, D K Hibberd, Karamjit Singh Jandu, D Lowe, M Pether, J Selway, G E Trantor

    Abstract:

    : A variety of isosteres of the DNA polymerase inhibitor Aphidicolin were synthesized as potential antiherpes agents. Modeling studies indicated that the bicyclooctane C, D rings of Aphidicolin could be replaced by an aromatic moiety while maintaining the spatial arrangement of the hydroxyl group equivalent to the essential C18 hydroxyl group of Aphidicolin. Of the racemic isosteres synthesized only 13, the compound with the greatest structural similarity to Aphidicolin, showed any significant antiviral activity in primary assays. An enantioselective synthesis of the compound was carried out and the 4aS isomer 36 was shown to account for the observed antiviral activity noted against herpes simplex virus 1 and human cytomegalovirus.

Olivier Hyrien – 3rd expert on this subject based on the ideXlab platform

  • Aphidicolin triggers a block to replication origin firing in xenopus egg extracts
    Journal of Biological Chemistry, 2001
    Co-Authors: Kathrin Marheineke, Olivier Hyrien

    Abstract:

    Abstract DNA replication origins are located at random with respect to DNA sequence in Xenopus early embryos and on DNA replicated in Xenopus egg extracts. We have recently shown that origins fire throughout the S phase in Xenopusegg extracts. To study the temporal regulation of origin firing, we have analyzed origin activation in sperm nuclei treated with the DNA polymerase inhibitor Aphidicolin. Sperm chromatin was incubated inXenopus egg extracts in the presence of Aphidicolin and transferred to a fresh extract, and digoxigenin-dUTP and biotin-dUTP were added at various times after Aphidicolin release to selectively label early and late replicating DNA. Molecular combing analysis of single DNA fibers showed that only a fraction of potential origins were able to initiate in the presence of Aphidicolin. After release from Aphidicolin, the remaining origins fired asynchronously throughout the S phase. Therefore, initiation during the S phase depends on the normal progression of replication forks assembled at earlier activated origins. Caffeine, an inhibitor of the checkpoint kinases ATR and ATM, did not relieve the Aphidicolin-induced block to origin firing. We conclude that a caffeine-insensitive intra-S phase checkpoint regulates origin activation when DNA synthesis is inhibited inXenopus egg extracts.