Glen Report 36-25: New Product Palmitate Serinol Phosphoramidite
Our serinol product line has been developed over the past few years through a strong collaboration with Glen Research and Nelson Biotechnologies.1
Currently, Glen Research offers a diverse range of serinol phosphoramidites and solid supports, including:
Five click chemistry products for oligonucleotide conjugation, including our latest addition, 3'-DBCO-Serinol CPG, introduced in this Glen Report
Three biotin products
Two dithiol products
Two amino modifiers
One fluorescein reagent
In this article, we are pleased to introduce Palmitate Serinol Phosphoramidite (Figure 1) to our product portfolio. This is the first serinol member to join our line of hydrophobic modifications, like fatty acids and cholesterol, which enhance cellular uptake and activity in various tissues. It is a serinol-based version of our Palmitate Phosphoramidite (10-1978).2
Figure 1. Palmitate Structures
The addition of the DMT group in the serinol version allows for the incorporation of the modification internally, or at the 3′-end of the oligonucleotide by using one of our universal supports. The DMT group also facilitates multiple incorporations of the modification.
Palmitate-modification of oligonucleotides continues to be popular. Since the introduction of Palmitate Phosphoramidite in May 2022,2 ongoing research has focused on improving cellular uptake and delivery of palmitate-oligonucleotide conjugates to specific tissues. This research has resulted in many new scientific publications. We have selected two of these publications to highlight. One approach improved siRNA delivery by attaching palmitate to the 5'-end of the sense strands targeting HPRT1 in HeLa cells. Additionally, the effectiveness of these palmitate-conjugated siRNAs was enhanced by using a synthetic sphingolipid analog, which inhibits endocytic recycling.3
In the second approach, a palmitate phosphoramidite monomer was synthesized and incorporated multiple times into antisense oligonucleotides (ASOs) using standard phosphoramidite chemistry. The addition of multiple palmitates increased the lipophilicity of the ASOs, which in turn enhanced their cellular uptake compared to ASOs without palmitate. The position of palmitate insertion within the ASO sequence also affected cellular uptake. Specifically, inserting two palmitates at the 5′-end of the ASO improved cellular uptake while placing one palmitate at the 5′-end and another at the 3′-end resulted in reduced cellular uptake compared to ASOs without fatty acids.4
Use of Palmitate Serinol Phosphoramidite
The Palmitate Serinol Phosphoramidite has an advantage over the Palmitate Phosphoramidite in that
it dissolves fully in acetonitrile, whereas the latter requires a mixture of acetonitrile and dichloromethane (1:3). Like the Palmitate Phosphoramidite, a 6-minute coupling time is recommended for the serinol version. No additional changes are necessary beyond the standard deprotection and cleavage methods required for the nucleobases.
References
The Glen Report, 2013, 25.1, 4-5.
The Glen Report, 2022, 34.1, 9-10.
B.T. Finicle, et al., Nucleic Acids Res, 2023, 51, 1583-1599.
Y. Tanaka, et al., Bioorg Med Chem, 2023, 81, 117192.
Product Information
