Design of 1,8-Naphthyridine Derivatives for Molecular Recognition of Guanine and Quadruplex DNA in Water
Date Issued
2011
Date
2011
Author(s)
Lu, Shao-Hung
Abstract
This thesis consists of two parts. The first part is molecular recognition of guanosine phosphates by ethynyl-linked aniline-naphthyridine conjugated molecules in water; the second part is to design and synthesize water-soluble receptors for binding with quadruplex DNA.
In the first part, the ethynyl-linked aniline-naphthyridene molecules (Sa-APENA、Diol-APENA、Ol-APENA and Am-APENA) were synthesized and used as the hydrogen-bonding receptors of a biologically important substrate Guanine. We investigated their photophysical properties and binding affinity. The receptors Sa-APENA and Am-APENA showed good and selective binding affinity for guanine derivative G-10. The binding caused fluorescence quench. The binding affinity is very high, Ka = 412,300 and 233,200 M–1 for Sa-APENA and Am-APENA, respectively, in CH2Cl2 solution. Compared with compound 4, compound 22 lacked for acetyl group is totally lose the selectivity between G-10 and A-10. It was quite obvious that the acetyl on 2-aminonaphthyridine is very important for distinguish purine derivatives. These molecules bind A-10 weakly, and the binding caused enhanced fluorescence. Compound 44, a naphthyridine derivative containing a pyrene moiety increased the binding affinity, Ka = 1,443,900 M–1 with guanine derivative G-10 through an additional π–π interaction. The naphthyridine dimer 55 with triazole linkers prepared by click chemistry was not preorganized, so that the binding affinity with guanine derivative G-10 was low, Ka = 185,500 M–1 in CH2Cl2 solution. On the other hand, the preorganized naphthyridine dimer 53 bound strongly to guanine derivative G-10, Ka = 1,809,700 M–1 in CH2Cl2 solution. These efficient fluorescent chemosensors are potentially useful in bioorganic researches.
In the second part, the water soluble naphthyridine derivative 64 and conjugated aromatic compounds 65, 66 and 67, which bear two di(2-pyridylmethyl)amine–Zn (DPA–Zn) functional groups, were synthesized. Compound 64 binds the anti-parallel quadruplex H24 selectively. The absorption showed a red shift from 372 nm to 392 nm with decreased absorbance. The fluorescence was also bathochromic by 68 nm. The binding did not change the quadruplex structure according to the CD spectrum. Compound 64 stabilized quadruplex structure and increased the melting temperature from 53.2 oC to 64.2 oC. Compound 65 bearing two DPA–Zn also stabilized quadruplex structure and increased the melting temperature to 62.0 oC. According to the polyacrylamide gel electrophoresis, compound 65 binds H24 in a high selectivity.
Subjects
Naphthyridine
Guanine
Quadruplex DNA
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-100-D95223012-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):385d2a88960bb95e02ecd71cb331a1a0