Testing the Predicted Enhancement in DNA Sequence Specificity and Binding Affinity of Formamido-pentaamides over their Formamido-triamide Counterparts
Dr. Moses Lee, Hope College
Dr. Balaji Babu, Hope College
Dr. Sameer Chavda, Hope College
Dr. Vijay Satam, Hope College
Polyamides that contain imidazole and pyrrole heterocycles are known to target the minor groove of DNA in sequence specific interactions. Such molecules have the ability to alter gene expression. Analogs of the naturally occurring product distamycin have been developed and shown to bind in stacked anti-parallel dimers, but range in their affinity and specificity towards their target sequences. Although the formamido group is usually omitted from these analogs, it has been found to be important in increasing affinity and binding site size. Various formamido triamides have been synthesized, with f-ImPyIm showing the greatest affinity in targeting its cognate DNA sequence, 5’-d(ACGCGT)-3’. The established pairing rules for minor groove recognition indicate that the formamido-pentaamide, f-ImPyImPyIm, should bind with greater specificity to its cognate sequence without sacrificing affinity. This also calls for the synthesis of f-PyPyPyPyPy, which would target the control sequence 5’-d(AAATTT)-3’. The focus of this research is directed towards the synthesis of f-ImPyImPyIm and f-PyPyPyPyPy and testing their affinity and specificity in comparison with their triamide counterparts.
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