York's new combinatorial chemistry facility lures scientists back to Canada

By Cathy Carlyle

Combinatorial chemistry is a technology for preparing compounds en masse simultaneously so that large numbers may be tested rapidly for desirable properties. Scientists hope that, by using the technology, the discovery of new drugs will be accelerated.

The field of combinatorial chemistry has created a bond with the minds of scientists around the world. The technology used is cutting edge - and York is at the forefront of promoting it in Canada through its new state-of-the-art facility.

The concept is about three decades old, but is relatively new in terms of application. Now, thanks to computer-controlled automation, hundreds, and even thousands, of compounds can be prepared per year by one chemist. The goal is to reduce the time it takes to develop a drug lead and make a product available to the public.

Chemistry Professor Michael Organ, Co-founder and Director of the new facility, has one big wish - that it will provide a strong pull for scientists who have left Canada, or who believe they need to leave the country, to pursue more technologically-advanced and lucrative jobs elsewhere.

Another hope is that drug leads prepared at the facility through combinatorial chemistry (combi-chem) will become drug candidates that can be used in the treatment of disease.

"We're competing with Goliath - the United States," Organ said. "I want to see Canada become strong and competitive in this field. That's partly why we have put this facility together - to compete globally with the large pharmaceutical companies that have been attracting academics away from our universities."

Organ, originally from Millgrove, Ontario, is proof that the brain drain can be reversed. He left his faculty position at the Purdue School of Science in Indiana in 1997 after hearing of exciting work underway in chemistry at York. In particular, he cited chemistry Professor Clifford Leznoff's pioneering work in the field of small molecule synthesis on solid support, work which continues today. Leznoff and chemistry Professor Ed Lee-Ruff are the other founding members of the Combinatorial Chemistry Facility.

In early June, President Lorna Marsden officially opened the new facility in the Chemistry and Computer Science Building, saying that "private sector partnership with government is essential." Organ heartily agreed with this statement. They were referring to an innovative concept which is at the facility's foundation. Academics, partly backed by government funding and private industry, are cooperating to make the concept work.

In fact, certain pharmaceutical and instrument manufacturing companies are founding partners. Some of the 15 scientists and technicians newly-hired in the facility are collaborating with pharmaceutical companies such as Eli Lilly Canada Inc., Glaxco Wellcome Inc., Allelix Biopharmaceuticals Inc. and Dalton Chemical Laboratories Inc. Others are working with precision scientific equipment manufacturers, MDS SCIEX and Bruker Canada Ltd.

Another interesting feature of the facility is that other universities and fledgling biotech companies that cannot afford the technology may use York's leading-edge combi-chem equipment. "It's very costly to acquire all these machines at once," said Organ. "Now Canadian companies are going to be able to overcome the exorbitant set-up costs by using our world-class Combinatorial Chemistry Facility."

At the opening ceremony, Chair of the Department of Chemistry Chester Sadowski said that York was able to purchase the approximately $2 million worth of specialized equipment with grants from the Canadian Foundation for Innovation and the Ontario Research and Development Challenge Fund (ORDCF). The latter provided a further $1 million to create researching positions at the facility.

Dean of the Faculty of Pure and Applied Science, Robert Prince, sees the new facility as a place where combinatorial chemistry research will be advanced. "It is now of great interest to the biotech sector, and provides the basis for a more vital Canadian industry in years to come," he said. "I am delighted to see Professor Organ's plans come to fruition."

Researchers in the new chemistry area hope to establish a library, not with books, but with collections of compounds. Organ, Leznoff and Lee-Ruff are committed to establishing closer ties with pharmaceutical companies so that they can continue to pursue pure and applied research. Their belief is that some of the compounds in their libraries will be biologically active to fight disease. Areas of interest under investigation in the facility at present include AIDS and disorders of the central nervous system.

"What we do is 'parallel' synthesis to prepare a 'library' of compounds derived by combining a wide variety of starting materials with one central building block to give a set of products that are as structurally diverse as possible. This is carried out simultaneously in separate 'wells' of a chemical reactor, so that each well contains a unique compound," explained Organ. "All the compounds thus produced are structurally similar but identifiably different, and form a 'family' of potential drug leads."

At this point, like detectives, scientists undertake a process to find the precise compound that is optimal for becoming a drug lead - that is, one that might eventually be able to be used to produce a treatment for a disease.

"This is achieved in collaboration with biochemists who screen the libraries for biological activity, to see which ones are active," said Organ. "Of course, of these leads - even promising ones - only one in tens of thousands will make it to the shelf.

"Combi-chem won't discover new drugs, per se. It is a means of synthesizing and purifying compounds to speed up the process of finding drug leads. The technology itself is complex, but the process is much faster than preparing one compound at a time by hand, so to speak. You could explain it like this: you used to wash dishes slowly by hand. Now you can leave a large load to be washed unattended overnight."

World leaders in the field of chemistry, both academic and industrial, witnessed the opening of the facility. They were also attending the annual meeting in Toronto of the Canadian Society of Chemistry and provided lectures at the combinatorial chemistry symposium organized by Organ.