Abstract:
:The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. The (18)F-radiolabeled polyamides were prepared by oxime ligation between 4-[(18)F]-fluorobenzaldehyde and a hydroxylamine moiety at the polyamide C terminus. Small animal PET imaging of radiolabeled polyamides administered to mice revealed distinct differences in the biodistribution of a 5-ring beta-linked polyamide versus an 8-ring hairpin, which exhibited better overall bioavailability. In vivo imaging of pyrrole-imidazole polyamides by PET is a minimum first step toward the translation of polyamide-based gene regulation from cell culture to small animal studies.
journal_name
Proc Natl Acad Sci U S Aauthors
Harki DA,Satyamurthy N,Stout DB,Phelps ME,Dervan PBdoi
10.1073/pnas.0806308105subject
Has Abstractpub_date
2008-09-02 00:00:00pages
13039-44issue
35eissn
0027-8424issn
1091-6490pii
0806308105journal_volume
105pub_type
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