Food scientists have sought a suitable replacement for table sugar for the past 100 years. However, it has been within the last 30 years that researchers have used modern techniques of computer modeling in the search for sugar’s replacement.
The working model of sugar receptors has evolved from a simple lock-and-key strategy, to a multi-faceted, malleable lock.
History of Artificial Sweeteners
The tale begins with the serendipitous discovery of Aspartame by a chemist, James M. Schlatter, at an unrelated laboratory. He took his experiences to G. D Searle and Company where he and two others were credited with the discovery Aspartame and its related analogues.
The workers at Searle devised a method of taste-testing the sweetness of the new substances. In manner reminiscent of Alchemists, the team revised the original discovery in ways to enhance the sweetness. The team realized that modifications to the molecule varied the sweetness. They ultimately used a method developed by medicinal chemists to analyze bio-active analogues: the Quantitative Structure Activity Relationship (QSAR). Not only could they formulate data tables—but they could graph their data in a ‘flow-chart manner.’
The Searle team realized their methodology could address how different molecules could be sweet but not resemble table sugar.
Sweet, But Not Sugar: The Chemistry Working Model
At about the same time as the Searle labs were developing Aspartame, a team from New York State Agricultural Experiment Station developed a working model of ‘sugar receptors in the human mouth.’
The researchers studied fructose, saccharine, chloroform, alanine and a substituted-benzene molecule for degrees of sweetness. They found that the key to sweetness was a weak chemical bond between adjacent sites on one (pseudo-)sugar molecule and their newly-proposed receptor site on the taste bud. The weak interaction is known to scientists as the hydrogen-bond.
The new model was ‘the working model’ for more than 20 years. It was a typical lock-and-key model; there were only a few variables to adjust if you were looking for a new sugar-substitute. However, it was finding the next sugar-substitute that presented a problem. The chemists knew how to vary the molecules – but what or where could/would they find ‘the lead molecule?’
A ‘lead molecule’ is the initial molecule that starts the chase to the invention. In the case of Aspartame, the initial discovery was serendipitous, and they didn’t find another.
Artificial Sweetener Chemistry: Finding a Lead Molecule
Thus, the outstanding question was how does one find a ‘lead molecule’? The scientists knew of a handful of sweeteners and every sweetener differed from the other. Thus, the chemists reasoned that the sugar receptor must be a virtual mirror of the how sugar-substitute itself looked.
When all of the so-called sugar-molecules are imposed upon one another, therein lies the AHA! moment. Molecules are always in motion, so the receptor may be malleable – and so can the sugar molecule.
This is why computer modeling is so helpful in the design and development of new sugars. The new model differed drastically from the simple lock-and-key model; the new technique had to employ hundreds of different potential motions between the candidate molecule and the receptor.
New Sweetener Advantame vs. Aspartame
Aspartame and its cousin Advantame are sugar substitutes comprised of two amino acids; phenyl alanine and aspartic acid. The amino acids exist alone naturally, but when combined, come together as a super-sweetener: Aspartame or Advantame. Advantame is a super-sweetener that is more resistant to digestion than its cousin because of the substitution upon the Nitrogen.
When the Searle team invented Aspartame, the scientific publication delineating its path showed that the team could adjust sweetness by varying one side of the molecule and not the other. They believed that no one would be able to duplicate their invention – but they were wrong.
Advantame FDA-Approved in May 2014
In May 2014, the FDA approved a new sweetener for public consumption: Advantame. This new sweetener is an analogue to Aspartame.
The development team from Ajinomoto North America modified the part of the molecule that the original Searle team believed would not alter the sweetness.
Although the modification method is presently a trade secret, it does not prevent others from studying the molecule.
Advantame: More Stable To Digestion?
Contrasting the new sugar analogue to the Searle discovery, one may infer the new discovery is more stable to digestion. By adding the molecular extension to nitrogen element of Aspartame, the inventors made the molecule more impervious to enzymes. And, the toxicology studies bear out this assumption as being true.
From Lock and Key to Computer Modeling: Possibilities are Endless
The search for the best sugar-replacement may never end – it’s a complex topic. Thanks to modern technology, the use of computer modeling, to replace chemistry’s lock and key strategy, has allowed researchers to make huge strides in food chemistry.