Nuclease resistant chimeric oligonucleotides

A method of enhancing the nuclease resistance of an oligomeric compound comprising providing at least one modified nucleoside at either the 3′ or 5′ terminus of said oligomeric compound to give a modified oligomeric compound of formula V:

• 77
• n is from 3 to about 50;
• each Y1 is, independently, an internucleoside linking group;
• Y2 is oxygen or an internucleoside linking group;
• Y3 is oxygen or an internucleoside linking group;
• each Bx is an optionally protected heterocyclic base moiety;
• each A1 is, independently, hydrogen or a sugar substituent group;
• W1 is hydrogen, a hydroxyl protecting group or a modified nucleoside selected from the group consisting of
• 78
• W2 is hydrogen, a hydroxyl protecting group or a modified nucleoside selected from the group consisting of
• 79
• each A2 is, independently, alkyl, alkenyl, alkynyl, aryl, alkaryl, O-alkyl, O-aryl, amino, substituted amino, —SH, —SA3, thiolether, F, or morpholino;
• each A3 is, independently, H, a sulfur protecting group, aryl, alkaryl, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, or alkaryl, wherein said substitution is OA5 or SA5;
• each A4 is, independently, H, a nitrogen protecting group, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, or alkaryl, wherein said substitution is OA5 or SA5;
• each A5 is, independently, hydrogen, C1-C10 alkyl, cycloalkyl or aryl;
• each V1 is, independently, O or S;
• wherein at least one of W1 and W2 is not hydrogen or a hydroxyl protecting group.