Modeling the preferred shapes of polyamine transporter ligands and dihydromotuporamine-C mimics: Shovel versus hoe

    Authors

    F. Breitbeil; N. Kaur; J. G. Delcros; N. Martin; K. A. Abboud;O. Phanstiel

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    J. Med. Chem.

    Keywords

    XESTOSPONGIA-EXIGUA KIRKPATRICK; BIOLOGICAL EVALUATION; MOLECULAR; REQUIREMENTS; PROTONATION CONSTANTS; SELECTIVE DELIVERY; MAMMALIAN-CELLS; NUCLEIC-ACIDS; SPERMIDINE; ANALOGS; MOTUPORAMINES; Chemistry, Medicinal

    Abstract

    Preferred conformers generated from motuporarnine and anthracene-polyamine derivatives provided insight into the shapes associated with polyamine transporter (PAT) recognition and potentially dihydrornotuporamine C (4a) bioactivity. Molecular modeling revealed that N-1-(anthracen-9-yli-nethyl)-3,3-triamine (6a), N-1-(anthracen-9-ylmethyl)-4,4-triamine (6b), N-1-(anthracen-9-ylmethyl)-N-1-ethyl-3,3-triamine (7a), N-1-(antliracen-9-ylmethyl)-N-1-ethyl-4,4-triamine (7b), and 4a all preferred a hoe motif. This hoe shape was defined by the all-anti polyamine shaft extending above the relatively flat, appended ring system. The hoe geometry was also inferred by the H-1 NMR spectrum of the free amine of 7a (CDCl3) which showed a strong shielding effect of the anthracene ring on the chemical shifts associated with the appended polyamine chain. This shielding effect was found to be independent over a broad concentration range of 7a, which also supported an intramolecular phenomenon. The degree of substitution at the NI-position seems to be an important determinant of both the molecular shape preferences and biological activity of anthracenylmethyl-polyamine conjugates.

    Journal Title

    Journal of Medicinal Chemistry

    Volume

    49

    Issue/Number

    8

    Publication Date

    1-1-2006

    Document Type

    Article

    Language

    English

    First Page

    2407

    Last Page

    2416

    WOS Identifier

    WOS:000236979100006

    ISSN

    0022-2623

    Share

    COinS