Phenylalanine dipeptide

The HIV-protease inhibitors, probably the most successful drugs used to prevent HIV turning into AIDS, are all protein mimics with an unreactive C-C bond replacing an amide link. That bond is marked with a broad arrow in norvir 152, Bristol-Myers Squibb s entry in this class. Amide disconnection reveals that the key central part of the molecule 154 looks like a phenylalanine dipeptide except that it has the C C bond. So can we make 154 from phenylalanine 4 ... 

The fundamental component of the system is again cyanamide, but for optimum yields, the addition of AICA HCl and high-energy phosphate (in this case ATP) is required. The amino acid solution with the other components is heated after evaporation, at temperatures which may vary from 40 to 90°C, for up to 24 hours. Upon separation by thin-layer chromatography the peptides are derivatized and identified by combined gas chromatography-mass spectrometry. After 1 hour reaction at 88°C the yield of L-phenylalanine dipeptide was 36% and that of the L-isoleucine dipeptide 22%. The yield and number of oligopeptides obtained from L-phenylalanine increased with temperature and time, with about 66% of the amino acid being converted to a mixture of di-, tri- and tetrapeptides in 24 hours at 90°C.< >... 

The same group have also produced another type of nucleopeptide hydroge-lator by joining a phenylalanine dipeptide with either one of the four major nucleobases, forming the compounds lA, IT, IG, IG [81]. Further conjugation of compound 1 with tyrosine phosphate yields compound 2, and compound 3... 

Digestion of the tetrapeptide of Problem 27 13 with chy motrypsin gave a dipeptide that on ammo acid analysis gave phenylalanine and valine in equimolar amounts What ammo acid sequences are possible for the tetrapeptide ... 

There are thousands of breweries worldwide. However, the number of companies using fermentation to produce therapeutic substances and/or fine chemicals number well over 150, and those that grow microorganisms for food and feed number nearly 100. Lists of representative fermentation products produced commercially and the corresponding companies are available (1). Numerous other companies practice fermentation in some small capacity because it is often the only route to synthesize biochemical intermediates, enzymes, and many fine chemicals used in minor quantities. The large volume of L-phenylalanine is mainly used in the manufacture of the artificial dipeptide sweetener known as aspartame [22389-47-0]. Prior to the early 1980s there was httle demand for L-phenyl alanine, most of which was obtained by extraction from human hair and other nonmicrobiological sources. 

Aspartame (1) is the primary nonnutritive sweetener used in carbonated soft drinks. It is approximately 200 times sweeter than sucrose. Aspartame is the methyl ester of a dipeptide of T.-phenylalanine and L-aspartic acid. 

One of the most interesting uses for cinnamic acid in recent years has been as a raw material in the preparation of L-phenylalanine [63-91-2] the key intermediate for the synthetic dipeptide sweetener aspartame (25). Genex has described a biosynthetic route to L-phenylalanine which involves treatment of immobilized ceUs of R rubra containing the enzyme phenylalanine ammonia lyase (PAT,) with ammonium cinnamate [25459-05-6] (26). 

Aspartame is a dipeptide, made up of aspartic acid and phenylalanine. Identify all the chiral atoms in aspartame and assign R/S stereochemistry to each. Is the stereochemistry the same as in the natural forms of aspartic acid andphenylalaninel... 

The same reagents can be used to form amides from carboxylic acids and amines, a method which is applicable to peptide synthesis. Condensation of A-benzyloxycarbonyl-L-phenylalanine and ethyl glycinate hydrochloride gave an 85% yield of purified dipeptide. 

Aspartame, a dipeptide (aspartic acid + phenylalanine) artificial sweetener marketed under the trade name Nutrasweet... 

Aspartame, N-a-L-aspartyl-L-phenylalanine methyl ester, trade names NutraSweet , and Aspartil , is a dipeptide derivative. Like dipeptides aspartame is metabolised into the constituents, i.e. amino acids and methanol. Therefore studies into the metabolic behaviour and the fate of metabolites were carried out. Levels of blood aspartate and glutamate were measured after intake of high aspartame doses. Changes were transient and allegations of influences of high aspartame levels on brain function could never be verified. 

Phenylalanine reacts with ninhydrin in the presence of a dipeptide (usually glycyl-L-leucine or L-leucyl-L-alanine) to form a fluorescent product. The fluorescence is enhanced and stabilized by the addition of an alkaline copper reagent to adjust the pH to 5.8 and the resulting fluorescence is measured at 515 nm after excitation at 365 nm see Procedure 10.2. 

Nitrophenyloxycarbonyl has not been a successful group in peptide chemistry, as dipeptide products are cyclized to the corresponding dike-topiperazines, but this is not the case with amino acid derivatives. Here, the free amino acids are obtained at >290 nm in very high yields [for example, 89% of L-phenylalanine from 3-(nitrophenyloxycarbonyl)-L-phenylalanine]. 

Aspartame is the most successful and widely used artificial sweetener. It is roughly 100 times as sweet as cane sugar. It is methyl ester of dipeptide formed from aspartic acid and phenylalanine. Use of aspartame is limited to cold foods and soft drinks because it is unstable at cooking temperature. 

During work on a series of aspartyl dipeptides containing ACC 71 (vide supra, Eq. (28), Sect. 4) at the carboxyl terminus, it was reported that dispartame Asp-ACC-OMe had a distinct sweet taste [302] and that the corresponding n-propyl ester had 250-300 times the sweetness of sucrose [303]. However, replacement of phenylalanine by 2,3-methanophenylalanine gave tasteless analogues of aspartame [293, 304], and some dimethyl-ACC 214 (methanovaline) and tri-methyl-ACC 215 aspartame analogues [Asp-(Me)n-ACC-OMe] have a bitter taste. These taste properties, which depend on the number and position of the methyl substituents, have been explained on the basis of topochemical models thus, a L-shaped conformation of the dipeptide is necessary for sweet taste, Eq. (86) [3051. 

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