Design of a new fluorescent probe: Pyrrole/imidazole hairpin polyamides with pyrene conjugation at their γ-turn

Fluorophores that are conjugated with N-methylpyrrole-N-methylimidazole (Py-Im) polyamides postulates versatile applications in biological and physicochemical studies. Here, we show the design and synthesis of new types of pyrene-conjugated hairpin Py-Im polyamides (1-5). We evaluated the steady state fluorescence of the synthesized conjugates (1-5) in the presence and absence of oligodeoxynucleotides 5'-CGTATGGACTCGG-3' (ODN 1) and 5'-CCGAGTCCATACG-3' (ODN 2) and observed a distinct increase in emission at 386 nm with conjugates 4 and 5. Notably, conjugate 5 that contains a p-alanine linker had a stronger binding affinity (K-D = 1.73 x 10(-8) M) than that of conjugate 4 (K-D 1.74 x 10(-6) M). Our data suggests that Py-lm polyamides containing pyrene fluorophore with a p-alanine linker at the gamma-turn NH2 position can be developed as the competent fluorescent DNA-binding probes. (C) 2012 Elsevier Ltd. All rights reserved.