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*****Glen Research Glen Report*****
Patrick Weiss, Xeragon AG
Xeragon AG and Glen Research Corporation introduce a novel and superior 2'-O-protecting group for automated RNA-synthesis, the TOM-Protecting-Group (patents pending):
FIGURE 1: STRUCTURE OF TOM-RNA MONOMERSTOM-PROTECTING-GROUP - A MAJOR IMPROVEMENT IN RNA SYNTHESIS
(1) A-TOM (2) C-TOM (3) G-TOM (4) U-TOM
The TOM-Protecting-Group is structurally related to the, so far, most successful tBDMS-Group introduced by Ogilvie and Usman in the early Eighties and is fully compatible to the established tBDMS-Chemistry used worldwide. This compatibility has the advantage that one can still use all known and already available modifications. Amidites, shown in Figure 1, containing the TOM-Protecting-Group are characterized by the features illustrated in Figures 2-5.
FIGURE 2: HIGH PERFORMANCE DUE TO MINIMIZED STERIC DEMAND
The TOM-Protecting-Group solves the problems encountered in automated RNA-synthesis due to the presence of a suitable spacer between the nucleoside and the silyl-group. This minimized steric demand of the TOM-Protecting-Group results in excellent coupling yields under DNA-coupling conditions, as illustrated in Figure 2 above.
FIGURE 3: FAST AND RELIABLE DEPROTECTION
The TOM-protecting group is removed easily and completely under mild conditions leaving the RNA completely intact, as shown in Figure 3. The short deprotection times result in minimized breaking of the strand during deprotection.
FIGURE 4: ABSENCE OF 2'-5' PHOSPHODIESTER LINKAGES IN THE OLIGO
The acetal structure of our TOM-Protecting-Group makes it completely stable towards basic and weakly acidic conditions and specifically prevents its migration from 2'-O to 3'-O (which would result in isomeric RNA, containing 2'-5'-phosphodiester linkages).
FIGURE 5: CRUDE PRODUCT OF AN 84mer ON CAPILLARY ELECTROPHORESIS
The synthesis of long and high yielding RNA-Molecules now becomes possible, as illustrated above.
The TOM-Protecting-Group is fully compatible with the established RNA-Chemistry, having the advantage of higher coupling yields and shorter coupling times. By making the TOM-Chemistry available to a large number of people, we hope to contribute to the field of RNA research and related areas.
Please contact Glen Research if you have any questions or comments!