Glen Report 20.111: Differences Between Universal Support II and III

What are the structural differences between US II and US III?

Universal Support II
Universal Support III
Figure 1: Universal Support Structures
Differences Between Universal Supports II and III

The universal linker, the top left section of structures 1 and 2 in Figure 1, is identical in Universal Support II and Universal Support III. The difference is in the attachment of the universal linker to the support. In the case of Universal Support II, the attachment is through a succinoyl diamide linkage while in Universal Support III it is a urea linkage. The amide assisted dephosphorylation reaction that releases the oligo-3'-OH into solution takes place in the universal linker section and the remainder of the attachment remains with the support after release of the oligonucleotide. So the structural differences have no effect on the function of the two supports and have no impact on the product oligonucleotide.

Why was the change necessary?

The synthetic changes described in this article were made to improve the control of the production of the universal support. In the case of Universal Support II, three reactions on solid phase are required and the quality analysis can only be carried out after these three steps. In the case of Universal Support III, the loading reaction is followed by simple capping of the support. The support can be analyzed after both steps. Clearly, the production of Universal Support III is under much more control and is also more amenable to scale up.

Why are the catalog numbers the same?

We have retained the same catalog numbers for Universal II and III since the difference only affects the support. (The situation is similar to lcaa-CPG, the core of most CPG supports, where individual manufacturers may use different structures for the long chain alkylamine (lcaa) linker.) All of our polymeric supports of this type have already been changed to the Universal Support III structure and the name and structure on the analytical data reflect this change. In future, CPG supports may also be changed if the benefits of the change are the same for CPG as for polymeric supports.

Can I make my own support?

The Carbomoylation Linker, (5) in Scheme 2, will be available commercially very shortly. The carbomoylation chemistry used to make the urea linkage is proprietary and details will be released as soon as the patent process is complete. In the meantime, the technology, Universal Support III and the carbomoylation technology required to produce the supports is available for licensing. Contact [email protected] for more information.

Has the performance of the support been affected?

Universal Support III performs identically to Universal Support II. However, since tighter control of production is possible, Universal Support III will always perform at the highest level previously achieved by Universal Support II.

Has the change affected my cost?

Cost is always paramount in everyone's mind when related to high throughput or large-scale oligonucleotide synthesis. The much improved synthesis of Universal Support III using the carbomoylation procedure also improved the cost structure. Universal Support III can be offered at about the same price as regular 2'-deoxynucleoside supports and at a lower price than ribonucleoside supports. Please contact us for a quotation.

Product Information

Universal Support II has been discontinued. Please see:

Universal Support III