The telomeric dG(GT)(4)G sequence can adopt a parallel-stranded double helical conformation

Oligonucleotides 3 ' -d(GTGTGTGTGG)-L-d(GGTGTGTGTG)-3 ' (hp-GT) and 3 ' -d( G(4S)TG(4S)TG(4S)TG(4S)TGG)-L-d(GGTGTGTGTG)-3 ' (hp-SGT), (L=(CH2CH2O)(3)), were shown by use of several optical techniques to form a novel parallel-s tranded tps) intramolecular double helix with purine-purine and pyrimidine- pyrimidine base pairing. The rotational relaxation time of hp-GT was simila r to that of a IO-bp reference duplex, and the fraction of unpaired bases w as determined to be similar to7%, testifying to the formation of an intramo lecular double helical hairpin by the sequence under the given experimental conditions. A quasi-two-state mode of ps-double helix formation was valida ted, yielding a helix-coil transition enthalpy of -135 +/-5 kJ/mol. The G(. )G and (TT)-T-. (or T-4S(.) T) base pair configurations and conformational parameters of the double helix were derived with molecular modeling by forc e field techniques. Repetitive d(GT) sequences are abundant in telomers of different genomes and in the regulatory regions of genes. Thus, the observe d conformational potential of the repetitive d(GT) sequence may be of impor tance in the regulation of cell processes.