Synthesis and biophysical studies of hairpin polyamides targeting the Brn-3b and GATA-3 transcriptional sites

[摘要] Hairpin polyamide analogs of distamycin A ( 1 ) were designed and synthesized to evaluate their ability to bind 5′-ATAGA-3′ and 5′-AGATA-3′ sequences which are important elements for controlling the function of the Brn-3b and GATA-3 transcriptional factors, respectively. The hairpin polyamides are composed of pyrrole and imidazole units linked together via a γ-aminobutyrate (GABA) unit. Hairpins 2b (Py-Py-Im-γ-Py-Py-Py) and 2c (Im-Py-Py-γ-Py-Py-Py) were synthesized to target the respective Brn-3b and GATA-3 cognate sequences. Preliminary biophysical studies including thermal denaturation and circular dichroism were performed and the results ascertained the binding of hairpins 2a and 2b to their respective cognate DNA sequences.

[学科分类] 内科医学

[关键词] Brn-3b;DNA;GATA-3;hairpin polyamides;minor groove;transcriptional factors