The present invention provides a method of synthesizing phosphoramidite
linkers that are useful for the production of synthesizing two or more
oligonucleotides in tandem. The inventive linker has the following
desirable properties: (i) enhanced stability to alkali conditions versus
the linkers previously published, (ii) cleaves to produce 5' and 3' ends
that are fully biologically compatible, (iii) cleaves completely under
conditions that are already used in cleavage/deprotection processes so it
is fully compatible with conditions that are common in laboratories and
does not require additives that necessitate further purification after
cleavage, (iv) integrates easily onto commercially available synthesizers
because it is compatible with standard coupling chemistry, and (v) is
compatible with DNA, RNA, forward, reverse, and LNA, synthesis
chemistries. In addition, the inventive linkers may be coupled to a solid
support. Thus, the inventive linkers provide a significant advancement in
the state of the art.