Title
Modeling the preferred shapes of polyamine transporter ligands and dihydromotuporamine-C mimics: Shovel versus hoe
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
DOI Link
Language
English
First Page
2407
Last Page
2416
WOS Identifier
ISSN
0022-2623
Recommended Citation
"Modeling the preferred shapes of polyamine transporter ligands and dihydromotuporamine-C mimics: Shovel versus hoe" (2006). Faculty Bibliography 2000s. 5980.
https://stars.library.ucf.edu/facultybib2000/5980
Comments
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