Blog
The Sweetest Accident in Peptide History: How a Licked Finger Revealed Aspartame
Few people think of aspartame as a peptide. It is one, though, and its discovery is one of the best accident stories in chemistry. In 1965, at a pharmaceutical company in Illinois, a chemist wetted his finger to turn a page and noticed an unexpected taste.
Key takeaways
- James Schlatter, a chemist at G. D. Searle, was making a tetrapeptide fragment of the hormone gastrin, in a search for an ulcer drug.
- One intermediate was the dipeptide aspartyl-phenylalanine methyl ester.
- Licking his finger to pick up a piece of paper, he tasted something intensely sweet.
- The compound is roughly 180 to 200 times sweeter than sugar by weight.
- Because it contains phenylalanine, products carry a warning for people with phenylketonuria.
A different project
Searle was searching for a drug to treat stomach ulcers. Gastrin, a peptide hormone that stimulates stomach acid, was a target, and Schlatter was synthesizing a short fragment of it, four amino acids long, as a possible inhibitor. Making that peptide meant building pieces and joining them, and one of the intermediate pieces was a small two-amino-acid molecule: aspartic acid joined to phenylalanine, with a methyl ester on the end.
The finger
The story, as Schlatter has told it, is simple. A little of the material had gotten onto his hands, and as he licked his finger to lift a piece of paper, he noticed a strong sweet taste. Tasting unknown chemicals is not recommended practice today, but he traced the taste to the dipeptide ester and recognized its potential.
What kind of peptide is it
Aspartame is the methyl ester of Asp-Phe, a dipeptide. In the body it is broken down by ordinary digestive enzymes into aspartic acid, phenylalanine and a little methanol. Because it is so sweet, a very small amount is needed. Its sweetness is a matter of shape: the molecule fits the sweet taste receptor on the tongue, a good illustration of how small peptide differences change receptor interactions. The L-Asp-L-Phe form tastes sweet, while versions with a mirror-image amino acid taste bitter or have little taste at all.
Regulation and stability
Aspartame was approved by the United States FDA for dry foods in 1981 and for carbonated drinks in 1983. It is not stable at high heat or for long periods in acidic liquids, because the ester and the peptide bond hydrolyze and the sweetness is lost. That behavior is a classic case of the chemistry in our pH stability post and hydrolysis hotspots.
Why the story matters for peptide research
- Short peptides can be potent in unexpected ways.
- Stereochemistry, which amino acid is the mirror image, can flip a molecule from sweet to bitter.
- Stability in solution is a design constraint for every peptide.
- Careful synthesis creates intermediates worth characterizing, a reminder of the value of good analysis.
The bottom line
Aspartame is evidence that the world of peptides is bigger than hormones and drugs. A two-amino-acid molecule turned out to be one of the most widely used food additives ever. For more on tiny peptides, see the three-amino-acid GHK story.
Related reading
- The GHK discovery story
- pH and peptide stability
- Hydrolysis hotspots
- Browse the full Research Library
Explore Lucid Aminos
- Shop all research compounds
- Read the lab reports (COA)
- Monthly Research Panel
- Frequently asked questions
- Partner program
- About Lucid Aminos
- Contact us
For laboratory research use only. Not for human or veterinary use, and not intended to diagnose, treat, cure or prevent any condition. This article is educational and is not medical advice.