-GLen research Corporation-



The Glen Research concept was based on our perception that the research community required a supply of novel reagents which, at first glance, may have seemed of little commercial value to the larger suppliers. We saw these esoteric products as the potential vehicles for the development of novel strategies for use in diagnostics, sequencing, and therapeutics. At the same time, we foresaw a need to provide products for routine oligonucleotide synthesis backed with quality specifications, analytical techniques and certification at the highest level.

The initial Glen Research offering in 1987 contained a complete set of reagents for DNA synthesis for cyanoethyl (CE) phosphoramidite chemistry which then was rapidly gaining acceptance. Modest though this range may have been, it was of major significance due to the Certificates of Analysis which accompanied every product. The analytical techniques and quality criteria used for the evaluation and acceptance of these reagents were to become an industry standard many years later.

This rather routine beginning was soon followed by the products which have become the Glen Research specialty: the largest selection of minor base phosphoramidites available and a potentially bewildering variety of reagents for oligonucleotide modification. To aid researchers in deciphering this array of products and to prompt them as to potential uses, the Glen Research Report was launched. Now published semi-annually as The Glen Report, this unique, valuable and respected newsletter has introduced an astonishing array of novel reagents while elucidating some complex chemical strategies and techniques. Today, Glen Research still offers far and away the widest selection of minor base phosphoramidites, modifiers and reagents for labelling oligonucleotides during the synthesis.

In 1989, Glen Research expanded into the delicate art of RNA synthesis, introducing the set of monomers still respected as the best available for the vast majority of applications. And, in 1990, we launched what was to become the most comprehensive range of products for the synthesis of the nuclease resistant variant 2'-OMe-RNA.

During 1993, Glen Research announced the Sterling line of products for DNA synthesis based on the highest criteria of quality, purity and reproducibility. Sterling grade is the level to which all other suppliers must aspire and which will lead the way to the development of oligonucleotide therapeutics.

As the market for oligonucleotides, modified and unmodified, continues to grow, Glen Research is committed to continuing to introduce novel reagents and techniques while maintaining our existing product mix and high level of customer service.



The list of minor base phosphoramidites offered by Glen Research is unique and comprehensive in its range. The uses applied by researchers to these monomers are extremely far-reaching, extending from structural analysis using X-ray crystallography and spectroscopic techniques, through mutagenesis studies and endonuclease assays, to triplex and antisense research. Of particular note is the commercial introduction of 5-propynyl-pyrimidine nucleoside phosphoramidites, under license from Gilead Sciences, Inc., which show tremendous potential in the development of antisense therapeutics. The minor base subset of our product line is a tribute to the ingenuity of our customers and we will continue to expand it to meet their needs.

With the launch in 1987 of a complete line of Amino- and Thiol-Modifiers, Glen Research has contributed to the development of a multitude of research techniques, including diagnostic probes after labelling with haptens or enzymes, attachment of oligos to solid supports for affinity chromatography or dot blot assays, and DNA sequencing. More recently, synthesis of labelled oligonucleotides has been greatly simplified by the emergence of phosphoramidites of the haptens themselves. For example, Glen Research currently produces biotin, fluorescein, psoralen, cholesterol, and DNP phosphoramidites. Glen Research supports this line of products with a comprehensive and well-referenced technical booklet User Guide to DNA Modification and Labelling.

Glen Research introduced its line of RNA monomers after a detailed review of the various protecting schemes available. Since their launch, these monomers have been applied successfully in a variety of RNA research environments. Our customers have reported excellent results in the synthesis of RNA used for: structural studies by spectroscopic analysis; analysis of ribozyme function; studies on structure and activity relationships in RNA viruses; hybridization studies; and ribonuclease assays. We acknowledge that even with these high-quality monomers, oligoribonucleotides are still difficult and time-consuming to produce and further work is continuing to improve synthetic procedures.

At an early stage, Glen Research noted the potential advantages of naturally occurring and nuclease resistant 2'-OMe-RNA. Although monomers for this chemistry proved to be difficult to produce, we now offer the widest variety of 2'-OMe-RNA monomers for use in antisense therapeutic and probe experiments, ribozyme studies, and other physical studies. In comparison to normal RNA, the ease of synthesis of 2'-OMe-RNA is remarkably improved with purification and isolation techniques identical to those used for DNA.

Modification of the phosphate backbone is an area of interest in the development of oligonucleotide therapeutics. Glen Research supports a variety of simple synthetic schemes. These include preparation of phosphorothioates during routine synthesis using a sulfurization step in place of the routine oxidation step, use of H-phosphonate monomers to prepare phosphoramidate or phosphotriester linkages, and the production of methyl phosphonate linkages using methyl phosphonamidite monomers.



Reagent quality in solid-phase synthesis is of paramount importance because of the excess used every cycle. Even trace impurities can exert a significant influence in the quality of the final product. Glen Research has always supplied detailed Certificates of Analysis to substantiate reagent quality, although providing this information is still resisted by many of the current reagent suppliers. Glen Research quality parameters, based on our understanding of the needs of solid-phase synthesis, remain the tightest in the industry. Since Glen Research reagents for the major DNA synthesizers are manufactured with such a high degree of production control and are analyzed to such tight specifications, they have been accepted as the ultimate in performance and quality.

Thus, in 1993, Glen Research accredited this important concept in a separate brochure introducing our Sterling grade. Every item in this line is produced using the highest quality materials available under the most stringent and reproducible conditions of manufacture. These criteria are supported with Sterling Certificates of Analysis that describe the rigorous analytical techniques and provide the actual analytical results. Sterling products are available for all major DNA synthesizers and include CE phosphoramidite monomers, synthesis columns, and all liquid reagents.

An ingenious modification of the protecting groups used in DNA synthesis offers a potentially significant improvement to existing techniques. By replacing benzoyl with acetyl as the protecting group for dC, synthesized oligos can be cleaved and deprotected in 10 minutes. This UltraFast deprotection scheme, originally developed by Beckman Instruments, Inc., promises to accelerate the production or PCR and sequencing primers without the need to change to novel and less well tried chemistry.

As we endeavor to improve on existing products for DNA synthesis, we focus on areas of weakness in the synthesis process. Our work on the redesign of synthesis columns has culminated in the development of TWIST™ columns for routine synthesis. In addition to being virtually leak-proof, TWIST columns allow users, if necessary, to gain access to the support simply by twisting off the retaining cap.

Purification and isolation of synthetic oligodeoxynucleotides remains the most time-consuming and labor-intensive portion of the synthesis process. We are happy to have participated in alleviating this production bottleneck with the introduction of the Poly-Pak™ group of DNA purification products. Poly-Pak cartridges allow users to purify and isolate synthetic oligos in a fraction of the time needed in the past. This technique has gained popularity with core facilities, commercial producers, as well as with individual researchers. Glen Research supports the technique with a comprehensive User Guide to DNA Purification.

TWIST and Poly-Pak are trademarks of Glen Research Corporation

Please contact Glen Research if you have any questions or comments!
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