CordenPharma gives collection of carbohydrate molecules

Partnership with CMO will allow GlycoNet researchers to work with a greater selection of oligosaccharides

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By Rebecca Medel

GlycoNet is pleased to announce a collaboration with CordenPharma International on a library of oligosaccharides.

“We are delighted that CordenPharma International will be partnering with GlycoNet by providing a collection of complex oligosaccharides for use in our Glycan Screening Core Service,” said GlycoNet Scientific Director Todd Lowary. “This contribution will substantially enhance our collection by adding a range of mammalian and microbial glycans, which will greatly facilitate the identification of ligands for carbohydrate-binding proteins relevant to the Network’s funded research programs.”

CordenPharma is a Contract Manufacturing Organization that was founded in 2006 with eight facilities throughout the US and Europe. It partners with pharmaceutical and biotechnology companies by equipping them with synthetic carbohydrates, glycolipids and glycopeptides.

“The collaboration with GlycoNet represents an important step in CordenPharma’s goal of becoming the recognized world leader in the manufacture of synthetic complex carbohydrates, including GMP and commercial production,” said Head of Operations US Stewart Campbell. “The brain trust and capabilities encompassed by GlycoNet will only enhance the already world-renowned Canadian carbohydrate research community and CordenPharma is proud to have the opportunity to participate in this worthwhile effort.”

The library of carbohydrates is an important contribution to the work of GlycoNet’s 25 funded research projects. It will include dozens of compounds covering a variety of carbohydrate classes including:

Glycosaminoglycans (GAG) from the heparin/heparan sulfate class ranging from di- to octasaccharides in size and with a variety of defined sulfation patterns.

Mammalian oligosaccharides (non-GAG)  (mono- to nonasaccharides) from the high-mannose class and the milk oligosaccharides class (LNFP-III, LnNT).

Microbe-related oligosaccharides based on known microbial polysaccharides, including Meningococcus B, Group A Streptococcus (hexa- and dodecasaccharides), poly-N-acetyl-glucosamines, Leishmania variable cap regions, and beta-glucans.

Taking on antibacterial resistance in the 21st century

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A summary of GlycoNet Network Investigators Eric Brown and Gerard Wright’s recently published work “Antibacterial drug discovery in the resistance era

By Rebecca Medel

We are in the midst of the resistance era for antibiotics, not quite a century after penicillin was discovered in 1929. Drugs meant to fight infections are fighting hard to even make it out of the lab and into the market—without much avail.

McMaster University researchers Eric Brown and Gerard Wright’s paper “Antibacterial drug discovery in the resistance era” published in Nature January 20, paints the picture we currently find ourselves in, the path we took to get here, and offers glimpses into the future of infection-fighting medicine.

The golden age of treating disease with antibiotics (including penicillin and the 1943 discovery of streptomycin) favoured natural products that are the source of most antibiotic medicine. But as they are chemically complex and difficult to derivatize, their use has fallen out of favour with most large pharmaceutical companies.

This golden age was followed by the medicinal chemistry era from the ‘60s to ‘90s when a transformation in medicine took place. Most pharmaceutical companies use the synthetic chemicals created during this time rather than the natural products of before, but their efficacy is at risk as the broad use of antibiotics in humans, animals and agriculture has created a great resistance among bacterial populations.

There are advantages and disadvantages stemming from both eras of research, but as Brown and Wright point out, “the overall result is a stalemate in discovery: screens of natural-product libraries identify bioactive but known compounds, and screens of synthetic libraries identify potent ligands of biochemical targets but with poor bioactivity.”

One solution they offer is the “development of synthetic libraries that capture the chemical diversity and physicochemical properties of natural products.” And another is to “capitalize on the ability of synthetic compounds to inhibit essential bacterial targets by developing delivery systems that solve the cell-envelope penetration and efflux challenges.”

In fact, known chemical scaffolds of natural products that have long been abandoned are being revisited in the hopes of finding a way to conquer bacterial resistance.

For the past two decades, the genes-to-drugs model has been in use, but despite advances in medicinal technology and computing, it has not led to the discovery of any new medicines. Brown and Wright point out that diseases that were once easily treatable have become deadly again. This fact, coupled with limited antibacterial drug discovery, has many, from scientists to the general public, accepting that we are in a crisis.

The authors are hopeful that looking to the history of antibiotic discovery, combined with a “fresh understanding of antibiotic action and the cell biology of microorganisms have the potential to deliver twenty-first century medicines that will be able to control infection in the resistance era.” But they do not deny that it will be challenging to develop new antibiotic drugs as the modern era of research has shown that “antibiotics that are highly effective, safe and broad spectrum are incredibly difficult to find.”