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Synthesis and Properties of Nonpolar DNA (Arylalkyl)phosphonates
Author(s) -
Amberg Stefan,
Engels Joachim W.
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200208)85:8<2503::aid-hlca2503>3.0.co;2-i
Subject(s) - chemistry , diastereomer , methylene , oligonucleotide , stacking , linker , alkyl , stereochemistry , fluorescence , dna , duplex (building) , thermal stability , crystallography , medicinal chemistry , organic chemistry , biochemistry , physics , quantum mechanics , computer science , operating system
The eight (arylalkyl)‐modified phosphoramidites (=(arylalkyl)phosphonamidites) 1 – 8 ( Fig. 2 ) were synthesized ( Schemes 1 – 3 ) and incorporated at different positions into 2′‐deoxyoligonucleotides. The [ P ( R )]‐ and [ P ( S )]‐diastereoisomers of the hexanucleotides 32 – 39 ( Table 1 ) and of the dodecanucleotides 41 – 45 ( Table 2 ) obtained were separated by means of reversed‐phase HPLC. UV, CD, and fluorescence spectroscopy were used to investigate the thermal stability ( T m ) and the structural changes of their DNA duplexes with 5′‐d(CGCGCG)‐3′ and 5′‐d(ATGATTGACCTG)‐3′, respectively. The T m values significantly depend on the place of modification ( Table 2 ). A dangling‐end effect is observed when the [3‐(anthracen‐9‐yl)propyl]‐modified 8 is attached at the 5′‐terminus (see duplex with 45c ). In the case of the incorporation of aromatic moieties tethered via a methylene linker to the P‐atom (benzyl‐ and (naphthalen‐1‐ylmethyl)‐modified 1 and 6 , resp.), the duplexes with the [ P ( R )]‐oligonucleotides are more stable than those with the [ P ( S )]‐isomers, whereas in the case of longer alkyl chains at the P‐atom (see 2 – 5 ), the T m values show the reverse tendency. The observed T m differences are assigned to changes in base stacking ( Figs. 6 and 7 ).