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M H Caruthers

Publications and source records attributed to M H Caruthers.

85 records · Page 5Linked to original sources
PubMedDate not supplied

Interactions between single-stranded DNA binding protein and oligonucleotide analogs with different backbone chemistries.

Chemical modification of backbone structures has been an important strategy in designing oligonucleotides capable of improved antisense effects. However, altered backbone chemistry may also affect the binding of oligonucleotides to key cellular proteins, and thus may impact on the overall biological action of antisense agents. In this study we have examined the binding of oligonucleotides having four different backbone chemistries to single-strand binding protein (SSB), a protein having a key role in DNA repair and replication. The oligomers tested had the same sequence, while the internucleoside linkages were phosphodiester (PO), phosphorothioate (PS), phosphorodithioate (PS2), or methylphosphonate (MP). We found that both PS and PS2 oligomers bound to SSB with higher affinity than PO oligonucleotides, while MP oligonucleotides did not bind appreciably at the concentrations tested. Oligonucleotide length was also an important factor in binding to SSB, but sequence was less critical. These observations indicate that backbone chemistry is an important factor in interactions between oligonucleotides and critical cellular proteins, and thus may be a key determinant of the biological effects of antisense oligonucleotides.

Binding, Competitive↗
PubMedDate not supplied

Inhibition of RNA cleavage but not polyadenylation by a point mutation in mRNA 3' consensus sequence AAUAAA.

A single U leads to G transversion in the 3' consensus sequence AAUAAA of the adenovirus early region 1A gene was constructed and the effect of this mutation on processing of the 3' end of the nuclear early region 1A RNAs was analysed. The results demonstrate that the intact AAUAAA is not required for RNA polyadenylation but is required for the cleavage step preceding polyadenylation to occur efficiently.

Adenoviruses, Human↗