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J Am Chem Soc. 2008 May 28;130(21):6859-66. doi: 10.1021/ja800888d. Epub 2008 May 7.

Next generation hairpin polyamides with (R)-3,4-diaminobutyric acid turn unit.

Author information

1
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.

Abstract

The characterization of a new class of pyrrole-imidazole hairpin polyamides with beta-amino-gamma-turn units for recognition of the DNA minor groove is reported. A library of eight hairpins containing ( R)- and ( S)-3,4-diaminobutyric acid (beta-amino-gamma-turn) has been synthesized, and the impact of the molecules on DNA-duplex stabilization was studied for comparison with the parent gamma-aminobutyric acid (gamma-turn) and standard ( R)-2,4-diaminobutyric acid (alpha-amino-gamma-turn)-linked eight-ring polyamides. For some, but not all, sequence compositions, melting temperature analyses have revealed that both enantiomeric forms of the beta-amino-gamma-turn increase the DNA-binding affinity of polyamides relative to the ( R)-alpha-amino-gamma-turn. The ( R)-beta-amine residue may be an attractive alternative for constructing hairpin polyamide conjugates. Biological assays have shown that ( R)-beta-amino-gamma-turn hairpins are able to inhibit androgen receptor-mediated gene expression in cell culture similar to hairpins bearing the standard ( R)-alpha-amino-gamma-turn, from which we infer they are cell-permeable.

PMID:
18459783
PMCID:
PMC3063708
DOI:
10.1021/ja800888d
[Indexed for MEDLINE]
Free PMC Article

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