Hybrid characteristics of oligonucleotides consisting of isonucleoside 2 ',5 '-anhydro-3 '-deoxy-3 '-(thymin-1-yl)-D-mmannitol with different linkagemodes

Oligonucleotides consisting of the isonucleoside repeating unit 2',5'-anhyd ro-3'-deoxy-3'-(thymin-1-yl)D-mannitol (4) were synthesized with the monome ric unit 4 incorporated into oligonucleotides as 1'-->4' linkage 4a (oligom er I) or 6'-->4' linkage 4b (oligomer II). The hybrid properties of the two oligonucleotides I and II with their complementary strands were investigat ed by thermal denaturation and CD spectra, Oligonucleotide I (4a) formed a stable duplex with d(A)(14) with a slightly reduced T-m value of 36.6 degre esC, relative to 38.2 degreesC for the control duplex d(T)(14)/d(A)(14), bu t oligomer II (4b) failed to hybridize with a DNA complementary single stra nd, The spectrum of the duplex oligomer I/d(A)(14) showed a positive CD ban d at 217 nm and a negative CD band at 248 nm attributable to a B-like confo rmation. Molecular modeling showed that in the case of oligomer I the C6' h ydroxy group of each unit could be located in the groove area when hybridiz ed to the DNA single strand, which might contribute additional hydrogen bon ding to the stability of duplex formation.