5’-Terminus Modifiers

Glen Research 5’-Modifiers are designed for use in DNA synthesizers to functionalize the 5’-terminus of the target oligonucleotide.  The 5’-Amino-Modifiers are available with a variety of chain lengths to fit exactly the desired application.

The DMS(O)MT-protected amino group is easier to deprotect compared to the MMT-protected one. The sulfoxy derivative survives conditions of oligonucleotide synthesis and can either be cleaved with standard deblock solution, or left intact for HPLC purification. At the same time, the DMS(O)MT group is fully compatible with cartridge purification.  When detritylation on a cartridge is carried out, the DMS(O)MT+, which is more stable than MMT+, does not reattach itself to an amine.  We now offer 5’-DMS(O)MT-Amino-Modifier C6 utilizing this new trityl based protecting group.   

5’-Amino-Modifier TEG, a hydrophilic triethylene glycol ethylamine derivative, is 12 atoms in length and fully soluble in aqueous media.

Our more recent 5’-amino modifiers, protected by a novel phthalic acid diamide (PDA) protecting group, are stable solids. In contrast to the TFA protected amino modifiers, which are viscous oils, the analogous PDA protected compounds are granular powders. This important property of these compounds allows straightforward handling, storage and aliquoting and leads to a significant increase in stability.  

Deprotection with methylamine in gas phase or aqueous solution or AMA leads to fast and complete removal of the PDA protecting group. However, ammonium hydroxide will not drive the equilibrium reaction to completion and only partial deprotection occurs - overnight deprotection with ammonium hydroxide will yield around 80% active amine.

We are offering three PDA Amino-Modifiers:

• 5’-Amino-Modifier C6-PDA

• Hydrophobic 5’-Amino-Modifier C12-PDA 

• Hydrophilic 5’-Amino-Modifier-TEG-PDA

The disulfide thiol modifier may be used for introducing 3’- or 5’-thiol linkages.  Dithiol Serinol, produced from lipoic acid and our patented serinol backbone, allows easy connection of multiply dithiol-labeled oligos to gold surfaces.  5’-Carboxy-Modifier C10 is a unique linker designed to be added at the terminus of an oligonucleotide synthesis.  It generates an activated carboxylic acid N-hydroxysuccinimide (NHS) ester suitable for immediate conjugation on the synthesis column with molecules containing a primary amine, resulting in a stable amide linkage.  An alternative carboxylate protecting group is the 2-chlorotrityl group, which is simply removed using the standard deblock cycle to generate a free carboxyl group on an otherwise fully protected oligonucleotide. The 2-chlorotrityl group is also removed during oligo deprotection with ammonium hydroxide or AMA and is incompatible with RP purification techniques.  PC Amino-Modifier is a photocleavable C6 amino-modifier, part of our line of photocleavable (PC) modifiers.  5’-AminoOxy-Modifier 11 is based on a tetraethylene glycol linkage for improved solubility and for reducing the potential negative impact on hybridization of the oligo.  The oxime formed from the reaction of alkyloxyamines with aldehydes creates a stable covalent bond.  In comparison, the imine formed by the conjugation of primary amines with aldehydes is not stable to acidic or basic conditions and requires subsequent reduction with borohydride to form stable amine conjugates.   5’-Maleimide Modifier Phosphoramidite, developed at the University of Barcelona, incorporates a maleimide cycloadduct that is stable to ammonium hydroxide at room temperature. This phosphoramidite can be incorporated into DNA and RNA with both phosphate and phosphorothioate linkages.  A retro–Diels-Alder reaction deprotects the maleimide immediately prior to conjugation.