Cell permeability of Py-Im-polyamide-fluorescein conjugates: Influence of molecular size and Py/Im content.
In order to investigate the influence of molecular size and pyrrole (Py)/imidazole (Im) content on the cell permeability of Py-Im-polyamide-fluorescein conjugates we systematically designed the Py-polyamides and Im-polyamides. Flow cytometric analysis revealed that Py-polyamides, even those with large molecular size, P-15 and P-18, showed good cellular uptake, but Im-polyamides showed very poor uptake. Fluorescence microscopy revealed that conjugate P-6 exhibited nuclear localization, while P-18 showed less nuclear stain but intracellular localization, suggesting that increased molecular size is one of the determinants in reducing nuclear access. Furthermore, results for hairpin polyamide conjugates H-1, H-2, and H-3 containing different Py/Im content indicated that cellular uptake increases as the Im residue is reduced. It appears that Py-Im-polyamide has general properties regardless of whether they have a linear or a hairpin structure.
Nishijima
Shigeki
S
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8501, Japan.
Shinohara
Ken-Ichi
K
Bando
Toshikazu
T
Minoshima
Masafumi
M
Kashiwazaki
Gengo
G
Sugiyama
Hiroshi
H
D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D002874:Chromosome Mapping; D019793:Fluorescein / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D020014:K562 Cells; D015394:Molecular Structure; D008970:Molecular Weight; D009757:Nylons / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D013237:Stereoisomerism; D014018:Tissue Distribution
D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; C096654:N-methylpyrrole; C018100:1-methylimidazole; D019793:Fluorescein