Modifications

For modified oligo pricing information see our Modifier Pricing Page.

  • To ensure freshness, we order most specialty reagents at the time your order is placed.  
    Please Contact oligos@yale.edu for quote.
  • We do not attempt to use leftover reagents as that may result in less than optimal coupling.
  •  We will incorporate most commercially available modifiers, not just those listed below, as long as it is particulate-free and non-radioactive.
  • Some modifications require a desalting step following synthesis which will be performed before delivery.

To avoid issues of improper storage and handling, we recommend allowing us to order the modified phosphoramidite/column. However, if you provide us with a commercially available phosphoramidite/column, our standard pricing will apply. If you would like to provide us with a phosphoramidite/column that is not commercially available, a surcharge for each different modification will apply.  This surcharge covers the additional labor costs of modified phosphoramidite/column handling and storage, synthesizer programming, oligo processing and e-mail correspondence. Also, since we are not supplying the modified phosphoramidite/column, our usual quality guarantee does not apply.

Modifications can be loosely divided into several groups:

  • backbone
  • internal
  • 5' terminal
  • 3' terminal

Two backbone modifications are presently available:

  1. phosphorothioate linkages which replaces one of the ether oxygens on the phosphate with a sulfur (giving equal amounts of the two resulting stereoisomers). This modification can be placed at any or all positions along the backbone and assessed a surcharge to cover additional labor in setting up and maintaining the synthesizer. 
  2. Methyl phosphonate linkages are also available but are quite expensive due to additional labor and reagent costs. Please inquire for pricing.

Many internal reagents can also be placed at the 3' end by using a universal synthesis support or a 3' phosphate column. Note also that 3' modifiers are only supplied only on 0.2 or 1.0 micromole columns.

Some modifications require the use of UltraMild columns, phosphoramidites and reagents that allow for mild cleavage and deprotection conditions. Some of these modifications include:

  • cyanine dyes including Cy3, Cy3.5, Cy5 and Cy5.5
  • TAMRA-dT and 3'-TAMRA
  • acridine
  • etheno-dA
  • 5,6-Dihydro-dU
  • 5'-iodo-dT
  • 5'-OH-dU
  • 5'-OH-dC
  • thymidine glycol

Please see our UltraMild Synthesis page for further details.

The following is a partial list of the more popular types of modifications that we offer. For other available modifications and pricing, please see the Glen Research web page (www.glenresearch.com) or E- mail us at oligos@yale.edu for more details:

  • Inosine and other partially selective or nonselective bases
  • 5' or 3' phosphate
  • Trimer Phosphoramidites (please inquire for pricing) 
  • LNA (Locked Nucleic Acid) incorporations (please inquire for pricing)
  • Primary amines, thiols: used primarily to link other groups (such as dyes) to the oligo post synthesis, but also used to block termini; available either for the 5' or 3' ends; amines also available attached to the base of thymidine for internal use.
  • Dyes: fluorescein and derivatives FAM, HEX, and TET; cyanine dyes; dabcyl; TAMRA; acridine; etheno-dA (Note: Unless a purification option is selected, oligos that contain cyanine dyes, TAMRA, acridine or etheno-dA are supplied cleaved, deprotected, and dissolved in 0.025 M potassium carbonate/MeOH/1M TEAA, and must be desalted before use. Please see our UltraMild Synthesis page for further details).
  • Halogenated deoxy and ribonucleotides
  • Spacers: various lengths of hydrocarbon chains or mixed polarity (ethylene glycol) linkers, or just plain ribose lacking a base
  • Biotin: either as a 5'-only moiety which couples very well, a biotin on a mixed-polarity linker (Biotin-TEG) which can be placed at either end or in the middle of an oligo, and Biotin-dT (biotin attached to one of the non base-pairing positions on thymidine)
  • Reverse synthesis: "Backwards" monomers enable us to synthesize in the reverse direction: 5' to 3'. We have used them to insert a normal monomer "backwards" in the molecule, and to block ends with a 3'-3' or a 5'-5' linkage.
  • Branches (symmetric or asymmetric): these enable you to increase the number of 5' ends (for example, to add more dye molecules to increase signal, or to have multiple oligos at one end linked to a single oligo at the other.
  • Dideoxy and other chain terminators
  • Cross-linking: psoralen

For modified oligo pricing information see our Modifier Pricing Page.