Modeling the preferred shapes of polyamine transporter ligands and dihydromotuporamine-C mimics: Shovel versus hoe
Abbreviated Journal Title
J. Med. Chem.
XESTOSPONGIA-EXIGUA KIRKPATRICK; BIOLOGICAL EVALUATION; MOLECULAR; REQUIREMENTS; PROTONATION CONSTANTS; SELECTIVE DELIVERY; MAMMALIAN-CELLS; NUCLEIC-ACIDS; SPERMIDINE; ANALOGS; MOTUPORAMINES; Chemistry, Medicinal
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 of Medicinal Chemistry
"Modeling the preferred shapes of polyamine transporter ligands and dihydromotuporamine-C mimics: Shovel versus hoe" (2006). Faculty Bibliography 2000s. 5980.