Synthesis of Oligonucleotides Containing 3‘-Alkylcarboxylic Acids Using a Palladium Labile Oligonucleotide Solid Phase Synthesis Support

Abstract
Oligonucleotides containing a 3‘-alkylcarboxylic acid are isolated using a Pd(0)-catalyzed cleavage reaction, in yields that are in most cases within experimental error of those isolated using standard oligonucleotide cleavage conditions (concentrated NH4OH). In contrast to results obtained with photolabile solid phase synthesis supports, no reduction in isolated yields of the oligonucleotides is observed when their length is increased from 20 to 40 nucleotides. The oligonucleotides are characterized by anion exchange HPLC, electrospray mass spectrometry, and enzymatic digestion. When methyl phosphoramidites are employed in the synthesis of the biopolymers, 3 serves as an orthogonal solid phase oligonucleotide synthesis support.