Aspartame (Nutrasweet®) is a remarkably sweet-tasting...

Question

Aspartame (Nutrasweet®) is a remarkably sweet-tasting dipeptide ester. Complete hydrolysis of aspartame gives phenyl alanine, aspartic acid, and methanol. Mild incubation with carboxypeptidase has no effect on aspartame. Treatment of aspartame with phenyl isothiocyanate, followed by mild hydrolysis, gives the phenylthiohydantoin of aspartic acid. Propose a structure for aspartame.

Accepted Answer

Hello everyone. Let's do this problem. It says Neo Tae is a dipeptide ester used as an artificial sweetener. The full hydrolysis of Neo Tae gives N 33 dimethyl butyl aspartic acid, Phey alanine and methanol treatment with carboxypeptidase enzyme shows no effect on neo tae edmund degradation of Neo Tae gives phenyl tho hydantoin derivative of N 33 dimethyl butyl aspartic acid suggest the structure for the neo. So, since Neo Ta is a dipeptide ester, that means it's made of two amino acids and it's also going to have an ester component. So let's discuss the processes that are mentioned in this problem. The treatment with carboxypeptidase enzyme and edmund degradation. So once we know how those processes work, we can make conclusions about the structure of Neo Tae based on these outcomes of the reactions of these processes with Neo Tae. So let's go through Edmund degradation and discuss what that is. So, edin degradation is the most efficient method for sequencing peptides, specifically end terminus peptides. And this is done first by treating the peptide with fenny isothiocyanate and then treating the peptide with acid hydrolysis or should I say performing acid hydrolysis of the peptide in this process. These two steps results in a shortened peptide chain and a Phey tho hydantoin derivative or P T H amino acid derivative fennel style. Hi Dan to derivative. So this is a derivative of the N terminal amino acid. And again, it's commonly referred to as the P T H amino acid derivative. So once we have this derivative of our N terminal amino acid derivative of in terminal oops, we can use chromatography maybe H P L C and we can compare the chromatography of the P T H derivatives of amino acid standards against the P T H derivative of our sample, right. So if we have the P T H derivative of our sample amino acid and we have the P T H derivatives of several amino acids that we know where those P T H S came from, right? We know the original amino acid, we can just match them up, right? So then we can identify the original in terminal amino acid that we started with in our sample, right? So that's how we can use edmund degradation to identify an N terminal amino acid. Let's talk about c terminal residue analysis which occurs with the treatment of carboxypeptidase enzyme that was discussed in the problem and it makes sense why we need one of each process, right? Because a dipeptide ester is going to be made of an N terminal amino acid and ac terminal amino acid. So the edin degradation took care of that n terminal amino acid identification. Now what about our c terminal analysis? We use that carboxypeptidase to cleave the sea terminus peptide bond in our amino acid. So I'm going to draw a quick amino acid, let me actually rewrite this Cleve c terminus peptide bond just so we have a better picture of what the amino acid looks like. So we have an end terminus, end our carbon with our, our group in our carbonyl group. And then we have our peptide bond connecting us to our c terminal amino acid. N H C hr two coo H OK. So on the right hand side, we have our c terminal amino acid which has the free carboxylic acid group. And then on the left hand side, we have that end terminal amino acid which has the free amino group. So notice that these amino acids are bonded at the opposite site that is stated in their name. So if the N terminal is free, that means it's bonded at the carboxyl site. If the C terminal is free, right, the carboxylic acid group is free, then that means it's bonded, the peptide bond is created at its amino site. All right. So in this residue analysis, carboxypeptidase is going to cleave that c terminus peptide bond. So c terminal, it'll cleave this peptide bond. So the end result is a shortened peptide and a free c terminal amino acid. And we can have subsequent reactions that keep cleaving the peptide bonds between amino acids and eventually the entire peptide is hydrolyzed to its individual amino acids. But there will be no reaction with carboxy pease if there is an absence of the free carboxylic terminal, right. And that's what the problem mentioned, right. It said treatment with carboxypeptidase enzyme shows no effect on neo tae. So that tells me that neo tae is going to have an absence of a free carboxylic terminal amino acid. So let's put together the two results of these processes. And the information we are given in the problem to speculate the structure of Neo ta which is a dipeptide ester according to the problem. So let's start with the edmund degradation results the edmund degradation according to the problem. Gave us the P T H derivative of N dye methyl beautiful aspartic acid. So that means that is our original amino acid. So let's draw N 3, 3 dimethyl bey aspartic acid. So since we said that edin degradation is used for N terminal amino acids, that means it's going to be bonded to the other amino acid at the carboxylic site. So let's draw N 33 dimethyl bey aspartic acid with a peptide bond coming out of the carboxyl site. So we'll have the carbonyl group that will be forming the peptide bond with the other amino acid. Then we have the carbon and the terminal amino group. So N H and we have a dimethyl bey group. So 1, 2, 3, four carbons, two methyl on carbon number three of that beauty group. And the R group, an aspartic acid is actually a carboxylic acid group. We have a carbon and then a carboxylic acid group. So don't get this confused with a free carboxyl group ac terminus amino acid because this is part of the carbon chain, right? If we look at our structure of the amino acid that we drew here, the carboxylic acid in the aspartic acid is part of this or group, right? OK. So there is our end terminal amino acid. What about the results of the sea terminal residue analysis? We had the problem tells us we have no reaction with carboxy Pepsid. So that means we're going to have an absence of the free carboxylic group coo H group or the free sea terminal, which means we're going to have an at the carboxy end of phenylalanine. That's where our methyl ester will be. So let's draw the peptide bond connecting to our phenyl alanine. And since that carboxylic acid group is supposed to be free in phenyl alanine, that means we are bonding this peptide bond to the amino site of phenyl alanine. So let's draw phenyl alanine peptide bonded to the aspartic acid derivative via its amino site and then add the methyl ester to the c terminus of phenylalanine. So we have the peptide bond bonded to fenny alanine amino site and then we have a carbon which we have in our group and then we have its carboxylic acid site except it is not free. That is where our is. And when hydrolyzed, this will form methanol, right? We have that metox group that will break off. And the R group here is that fenny group for Phey alanine. All right. So we have the three parts of our structure, the methyl ester pheno alanine and in 3, 3 dye methyl, beautiful aspartic acid. And that is the structure of Neo Ta. That's it for this problem. I hope this video was helpful and thank you for watching.

Key Concepts

Dipeptide Structure

Hydrolysis of Peptides

Phenylthiohydantoin (PTH) Derivatization

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