Oligonucleotide Synthesis for Therapeutics

TheraPure phosphoramidites for oligonucleotide therapeutics

Accelerate your oligonucleotide synthesis and development with a wide variety of Thermo Fisher Scientific phosphoramidites and tools. Our expert product support team is available to guide your screening, development, manufacturing and beyond, ensuring you have the most efficient and reproducible path to commercialization. Take your oligonucleotide synthesis project from early research to preclinical candidate with a single supplier that understands your needs every step of the way.

Oligonucleotide synthesis

Oligonucleotide therapeutics are a new class of drugs comprised of short strings of synthetic nucleotides. Oligonucleotide synthesis is a chemical pathway sequentially incorporating phosphoramidites to grow specific sequences of modified and unmodified DNA or RNA. The resulting molecules can then be used in a variety of applications including forensic and diagnostic assays (PCR, qPCR, and other platforms), nucleic acid therapeutics (RNAi, antisense, aptamer, CRISPR), and basic research (Figure 1).

Figure 1. A schematic diagram outlines the phosphoramidite oligonucleotide solid phase synthesis method.

Reagents for oligonucleotide synthesis

Thermo Fisher Scientific offers a range of phosphoramidites and solid supports for oligonucleotide synthesis:

DNA Phosphoramidites

TheraPure DNA phosphoramidites, the original brand of amidites designed specifically for therapeutic strategies
Continued development focuses on demand for high-sensitivity assays and next-generation therapeutic molecules

RNA Phosphoramidites

TheraPure RNA phosphoramidites are the gold standard for development and manufacturing of RNA-based therapeutic oligonucleotides
Includes 2’-modified RNA phosphoramidites to help increase stability and improve resistance to nuclease activity in vivo

2’ O-methyl (OMe) RNA Phosphoramidites

Traditional staple for oligo therapeutics for many years
Support novel technologies such as CRISPR-Cas9 gRNA
Key component of oligonucleotides designed for antisense, siRNA, aptamer, or gRNA-based applications
Modifications offer:
- Nuclease resistance
  - Fewer off-target effects
  - Increased hybridization affinities
- Faster deprotection with modified version including PAC-A and iPrPAC-G

2’ O-methyoxy-ethyl (MOE) RNA Phosphoramidites

Advanced generation of antisense oligonucleotides and siRNA designs
Key component of antisense-based oligonucleotides
Modifications offer:
- Nuclease resistance
  - Fewer off-target effects
  - Increased hybridization affinities

2’ Fluoro (Fl) RNA Phosphoramidites

Modifications support stability and affinity for oligos used in therapeutic strategies
Recently upgraded to meet standards of TheraPure products
Modifications offer:
- Nuclease resistance
- Increased thermal stability of RNA duplexes

Linkers and Spacers

3′, 5′, and internal oligo linkers are modifications used for NHS ester conjugation
Spacers increase the distance between functional groups, and provide conformational support

Structural Phosphoramidites

Used for molecular diagnostics and research applications
Modifications for design of primers, probes, or for structural studies
Modifications includes 5m-dC, dU, dI, N6-Me-dA, N4-Ethyl-dC, 8-oxo-dG, and more

Customization for oligonucleotide synthesis

Custom chemistries (e.g., triphosphate, phosphoramidites, and custom organic), customized QC, and packaging options including filling and labeling are available.

Customization options available on sugar, base or 5’ protection modification

Dimethoxy (DMT) substitution with alternate protecting groups
Base = A, C, G, T, or U protection modifications or base modifications
Sugar 2’ position modifications and protection options
Phosphoramidite, succinate, and support attachment and proprietary chemistries

Thermo Scientific TheraPure phosphoramidites

Originally designed specifically to meet the needs of oligonucleotide synthesis and development, TheraPure phosphoramidites are now important for therapeutics, molecular assay, and gene synthesis applications, which benefit from low levels of critical impurities. Our Thermo Scientific TheraPure phosphoramidites are designed for oligonucleotide manufacturers requiring highly defined impurity profiles and strictly controlled processes.

DNA Phosphoramidites

dA(Bz) CEP

dC(Bz) CEP

dG(iBu) CEP

dT CEP

Click images to enlarge

	dA(Bz) CEP	dC(Bz) CEP	dG(iBu) CEP	dT CEP
Cat. No.	27-2030	27-2032	27-2034	27-2036
Formula	C₄₇H₅₂N₇O₇P	C₄₆H₅₂N₅O₈P	C₄₄H₅₄N₇O₈P	C₄₀H₄₉N₄O₈P

RNA Phosphoramidites

Bz-rA CEP

iBu-rG CEP

Ac-rC CEP

rU CEP

Click images to enlarge

	Bz-rA CEP	iBu-rG CEP	Ac-rC CEP	rU CEP
Cat. No.	27-1903	27-1906	27-1805	27-1804
Formula	C₅₃H₆₆N₇O₈PSi	C₅₀H₆₈N₇O₉PSi	C₄₇H₆₄N₅O₉PSi	C₄₅H₆₁N₄O₉PSi

2’-MOE RNA Phosphoramidites

2-MOE-A CEP

2-MOE-5mC CEP

2-MOE-G CEP

2-MOE-5mU CEP

Click images to enlarge

	2′-MOE-A CEP	2′-MOE-5mC CEP	2′-MOE-G CEP	2′-MOE-T CEP
Cat. No.	27-1019	27-1020	27-1022	27-1021
Formula	C₅₀H₅₈N₇O₉P	C₅₀H₆₀N₅O₁₀P	C₄₇H₆₀N₇O₁₀P	C₄₃H₅₅N₄O₁₀P

2’-Fluoro RNA Phosphoramidites

Click images to enlarge

2′-Fluoro-Bz-A-CEP

2′-Fluoro-U-CEP

2′-Fluoro-iBu-G-CEP

2'-Fluoro-Ac-G-CEP

2′-Fluoro-Ac-C-CEP

	2′-Fluoro-Bz-A-CEP	2′-Fluoro-iBu-G-CEP	TheraPure 2′-Fluoro-Ac-C-CEP	TheraPure 2′-Fluoro-U-CEP	TP 2'-Fluoro-Ac-G-CEP
Cat. No.	27-1601	27-1607	27-1604	27-1602	SY5410*
Formula	C₄₇H₅₁FN₇O₇P	C₄₄H₅₃FN₇O₈P	C₄₁H₄₉N₅FO₈P	C₃₉H₄₆FN₄O₈P	C₄₂H₄₉FN₇O₈P

* For more specification details, contact us.

2’ O-methyl (OMe) RNA Phosphoramidites

2′-OMe-Bz-A-CEP

2′-OMe-U-CEP

2′-OMe-iBu-G-CEP

2′-OMe-Ac-C-CEP

Click images to enlarge

	2′-OMe-Bz-A-CEP	2′-OMe-U-CEP	2′-OMe-iBu-G-CEP	2′-OMe-Ac-C-CEP
TheraPure phosphoramidites' Cat. No.	27-2042	27-2044	27-2046	27-2043
Formula	C₄₈H₅₄N₇O₈P	C₄₀H₅₆N₇O₉P	C₄₅H₅₆N₇O₉P	C₄₂H₅₂N₅O₉P

Enabling oligonucleotide synthesis and development

Manufacturing excellence and expertise

With over 4 decades of engineered nucleic acid manufacturing experience, phosphoramidites combine our expertise in protection chemistries, modifications, manufacturing scale-up, and innovative purification strategies. All catalog (and custom) phosphoramidites are manufactured in our state-of-the-art Milwaukee, WI manufacturing facility, with an ISO 9001:2015 certified quality management system.

Quality manufacturing and regulatory documentation

Processes are monitored from material procurement through final QC and product release, providing batch-to-batch reproducibility. Our rigorously controlled manufacturing processes minimize levels of reactive P(III) impurities which could be incorporated into the oligonucleotide during synthesis and result in the accumulation of by-products. TheraPure phosphoramidites from Thermo Fisher Scientific are designed for pharmaceutical manufacturers looking for core building blocks to use in research and manufacturing. These reagents are crafted in facilities with thoroughly documented quality systems and audited by accredited registrars.

Interview videos

Watch our scientists discuss a variety of topics covering Thermo Fisher Scientific's Milwaukee site history, customer partnership, manufacturing process, quality improvement, mitigation of supply chain issues, and response to global needs.

Resources

Brochure

Phosphoramidites for Oligonucleotide Synthesis

Flyer

Guide

For Research Use Only. Not for use in diagnostic procedures.

Not Found