The present invention provides phosphoramidite linkers that are useful for the production of synthesizing two or more oligonucleotides in tandem. The inventive linkers have the following desirable properties: (i) enhanced stability to alkali conditions versus the linkers previously published, (ii) cleave to produce 5′ and 3′ ends that are fully biologically compatible, (iii) cleave completely under conditions that are already used in cleavage/deprotection processes so they are fully compatible with conditions that are common in laboratories and do not require additives that necessitate further purification after cleavage, (iv) integrate easily onto commercially available synthesizers because they are compatible with standard coupling chemistry, and (v) are compatible with DNA, RNA, forward, reverse, and 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.
Methods of synthesizing chemically cleavable phosphoramidite linkers
申请人:Anderson Keith
公开号:US20090048436A1
公开(公告)日:2009-02-19
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.