Linkers and co-coupling agents for optimization of oligonucleotide synthesis and purification on solid supports

A method for synthesizing oligonucleotides comprising:

• a) providing
• i) a substrate;
• ii) a plurality of non-cleavable linkers;
• iii) a plurality of anchor moieties, wherein said anchor moieties comprise the structure —C(X)—C(Y), wherein X comprises —OPO2O—, Y is a nucleophile and wherein said structure is part of a ring moiety;
• and
• iv) nucleotide monomers;
• b) derivatizing said substrate with said plurality of non-cleavable linkers;
• c) attaching said anchor moieties to said non-cleavable linkers;
• and
• d) synthesizing a oligonucleotide on said plurality of anchor moieties from said monomers.

A method for synthesizing oligonucleotides comprising:

• a) providing
• i) a substrate;
• ii) a plurality of non-cleavable linkers;
• iii) a plurality of anchor moieties, wherein said anchor moieties comprise the structure —C(X)—C(Y), wherein X comprises —OPO2O—, Y is a nucleophile and wherein said structure is part of a ring moiety;
• and
• iv) nucleotide monomers;
• b) derivatizing said substrate with said plurality of non-cleavable linkers;
• c) synthesizing a oligonucleotide on said plurality of anchor moieties from said monomers;
• and
• d) attaching said anchor moieties to said substrates;
• and
• e) synthesizing a oligonucleotide on said plurality of anchor moieties from said monomers.

A method for synthesizing oligonucleotides comprising:

• a) providing
• i) a substrate;
• ii) a plurality of stable linkers;
• iii) a plurality of anchor moieties;
• and
• iv) nucleotide monomers;
• b) derivatizing said substrate with said plurality of stable linkers;
• c) attaching said anchor moieties to said stable linkers, wherein said anchor moieties are attached to said linkers via coupling a 5′ phosphoramidite present within said anchor moieties to said linkers through a 5′-O—P-linkage;
• d) attaching said nucleotide monomers to said stable linkers attached to said anchor moeities through an anchor 3′-O—P—O-3′ nucleotide attachment thereby creating a plurality of anchor 3′-O—P—O-3′ nucleotide moeities;
• and
• e) synthesizing oligonucleotides on said plurality of anchor-nucleotide moieties from said monomers,
• wherein anchor 3′-O—P—O-3′ nucleotide phosphodiester attachments are cleaved by a ribonuclease.