Title

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

Authors

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