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2'-O-methoxyethyl ribose

2'-MOE

2'-O-methoxyethyl gapmers and steric blockers

In a 2'-MOE nucleotide the 2'-hydroxyl of the ribose carries a methoxyethyl group. The substituent shifts the sugar toward the C3'-endo pucker that RNA itself adopts, so a 2'-MOE residue binds a complementary RNA more tightly than the same residue as DNA, and it resists nuclease digestion. The methoxyethyl group is larger than the methyl group of 2'-OMe, and it confers more nuclease resistance.

A 2'-MOE residue is not itself a substrate for RNase H. RNase H1 cleaves the RNA strand of a DNA/RNA duplex, and a 2'-modified sugar makes the duplex RNA-like at that position, where it is not cut. A knockdown design therefore carries 2'-MOE in the wings of a gapmer and leaves a central gap of DNA, described below. Modified at every position, with no gap, a 2'-MOE oligonucleotide recruits no RNase H and acts as a steric blocker instead.

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Designed by AUM against your target, or made to your sequence by quotation.

Delivered yield nmol
  1. 5
  2. 10
  3. 25
  4. 50
  5. 100
  6. 200
  7. 250
  8. 500
  9. 1000
Order 2'-MOE against a targetOrder 2'-MOE to your sequence

Use

Applications and selection

  • RNase H knockdown

    A gapmer recruits RNase H1 to the target transcript, which is cleaved opposite the DNA gap. The design is made to the customer's target or to a sequence the customer sends.

  • A published design, reproduced

    2'-MOE gapmers are published in cell culture and in animals, so a design taken from the literature can be made to the same pattern, position by position.

  • A validated sequence, remade

    A sequence validated earlier is ordered again at another yield or purification tier, with no design step.

  • What it is not used for

    A very short oligonucleotide, or a target region so structured that only a short window is accessible: locked nucleic acid gives more affinity per residue there.

Design

Design notes

The gapmer. Two wings of 2'-MOE nucleotides flank a central gap of unmodified deoxynucleotides. The wings raise affinity for the target and protect the ends of the oligonucleotide from exonucleases; the gap forms the DNA/RNA duplex that RNase H1 recognizes, so the enzyme cleaves the target there. The gap must stay DNA and be several nucleotides long: a gap that is too short is not cut, and a design with no gap is a steric blocker. Write out which positions are 2'-MOE and which are DNA when you send the sequence.

The backbone. Gapmers are typically made on a phosphorothioate backbone, in which one non-bridging oxygen of each phosphate is replaced by sulfur. Phosphorothioate linkages resist nucleases and bind proteins, which supports uptake into cells and tissue, and they lower the affinity of the duplex slightly; a phosphodiester backbone is digested quickly in serum. At high concentration a phosphorothioate backbone can also raise toxicity.

Length and affinity. A 2'-MOE gapmer is an antisense oligonucleotide of conventional length, and its affinity comes from the sum of the wings rather than from a few very strong residues. Where the accessible window on the target is short, or the region is structured, locked nucleic acid wings reach the same affinity in fewer positions.

Purification and yields

Purification and study model

Desalt and RPC are sold for cellular studies. HPLC, the grade bought for animal work, is sold for in vivo studies.

Delivered yield nmol
  1. 5
  2. 10
  3. 25
  4. 50
  5. 100
  6. 200
  7. 250
  8. 500
  9. 1000
Purification and study model
PurificationStudy model
desaltin vitro, cellular studies
RPCin vitro, cellular studies
HPLCin vivo, animal studies

Delivered yield is what arrives in the tube, in nmol, not the amount synthesized to produce it. This chemistry is sold at every yield in every tier, so the tier and the yield are chosen independently.

Order 2'-MOE against a targetOrder 2'-MOE to your sequence

Related

Beside this chemistry

For research use only. Not for use in diagnostic or therapeutic procedures.