US Patent:
20140142253, May 22, 2014
Inventors:
- Wilmington MA, US
Santhosh Kumar Thatikonda - Woburn MA, US
Sant K. Srivastav - Burlington MA, US
Praveen K. Shukla - Burlington MA, US
Alok Srivastava - Burlington MA, US
Assignee:
ChemGenes Corporation - Wilmington MA
International Classification:
C07F 9/6553
C07H 21/00
US Classification:
5253335, 549 7, 536 265, 536 2531
Abstract:
The thiol modified oligonucleotides have vast number of applications in the field of nucleic acid chemistry. The conjugates generated by mono thiol groups are unstable at higher temperature, in high salt concentration buffers and in presence other thiols. There is strong need to develop a novel thiol modifier probes that can generate multiple thiol groups. Described herein are efficient processes and compounds, dithiolane phosphoramidites derivative and dithiolane succinyl supports. The advantage of our cyclic disulfide thiol modifier is multifold a) each incorporation introduces two thiol groups; b) it can be introduced at any desired site of oligonucleotides; c) The symmetrical branching nature of the spacer in the linker arm of dithiolane allows for clean oligo synthesis, where cleavage of the linker arm and thereby of loss of oligo chain is prevented. We have successfully made 20-mer oligonucleotide containing single dithiolane derivative at 3′, and 21-mer oligonucleotides containing single dithiolane derivative at 5′ or in the middle of the mixed base sequence. HPLC and ESI MS analysis of these oligonucleotides indicated satisfactory purity and correct composition of these oligos, respectively.
