The Indole Group of Tryptophan

The indole group of tryptophan is inert to activation and aminolysis reactions, so it does not have to be protected for constructing a peptide. It is sensitive, however, to 

FIGURE 6.9 The side chain of tryptophan has as a tendency to undergo reaction at the electron-rich centers indicated (A) oxidation in acidic medium,29 and (B) electrophilic addition by one or more carbo30 or arylsulfonyl cations. 

WE Savige, A Fontana. New procedure for the oxidation of 3-substituted indoles to oxyindoles. (preparative oxidation) J Chem Soc Chem Commun 599, 1976. 

L Kisfaludy, P Sohar. terf-Butylation of the indole ring of tryptophan during removal of the fert-butyloxycarbonyl group in peptide synthesis. Hoppe Seyler s Z Physiol Chem 359, 1643, 1978. 

Y Nishiuchi, H Nishio, T Inui, T Kimura, S Sakakibara. // -Cyclohexyloxycarbonyl group as a new protecting group for tryptophan. Tetrahedron Lett 37, 7529, 1996. 

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Protection of pyrroles and indoles. These heterocycles undergo t-butoxycar-bonylation in 80-95% yield on reaction with 1 and a catalytic amount of DMAP in acetonitrile. The Boc group is cleaved almost instantaneously by TFA at 25°.1 The same conditions are useful for protection of the indole group of tryptophan.2 Primary amino acid esters can be converted into bis(Boc) derivatives, and amino groups of peptides also undergo t-butoxycarbonylation.3... 

Indole Groups. The indole group of tryptophan is susceptible to substitutions and to oxidative cleavage by several different reagents (see Figure 7). Less reactive than such nucleophiles as thiol and amino groups, and frequently located within the interior of protein molecules, tryptophans are unaffected by many commonly used reagents. 

Tryptophane reactions. There are several tryptophane reactions one of these consists in the development of a violet color when a solution of protein which contains tryptophane is treated with glacial acetic acid and concentrated sulfuric acid. It is explained by the fact that the ordinary acetic acid contains glyoxylic acid, HOC—COOH, in small amounts, and this aldehyde-acid reacts with the indol group of tryptophane. The same color is given by glyoxylic acid. Proteins which do not yield tryptophane do not give this color. 

Intrinsic protein fluorescence originates with the aromatic amino acids. tryptophan (trp), tyrosine (tyr). and phenylalanine (phe) (Figure 3.1). The indole groups of tryptophan... 

Intrinsic fluorophores are naturally occurring whereby the intrinsic fluorescence originates within the aromatic amino acids such as tryptophan, tyrosine, and phenylalanine. The indole groups of tryptophan residues are the dominant source of UV absorbance/emission in proteins. 

The indole group of tryptophan (Trp) has a higher molar extinction coefficient than the phenolic and phenyl side chains of tyrosine (Tyr) and phenylalanine (Phe), respectively (see Table 1, Chapter 12). Thus although its quantum yield is similar to that of lyr, its fluorescence emission is much mote intense. Furthermore, its excitation spectrum overlaps the emission spectrum of Tyr and therefore fluorescence resonance energy transfer (FRET, see Chapters 2 and 3) from lyr to Trp occurs readily when both residues are in close proximity (i.e. located in the same protein molecule) and favourably orientated. The intrinsic fluorescence of a protein is therefore dominated by the contribution from Trp... 

A Karlstrom, A Unden. Protection of the indole ring of tryptophan by the nucleophile-stable, acid-cleavable /V "-2,4-di methyl pen t-3-yloxycarbonyl (Doc) protecting group. J Chem Soc Chem Commun 1471, 1996. 

In the tryptophan branch (Fig. 22-17), chorismate is converted to anthranilate in a reaction in which glutamine donates the nitrogen that will become part of the indole ring. Anthranilate then condenses with PRPP. The indole ring of tryptophan is derived from the ring carbons and amino group of anthranilate plus two carbons derived from PRPP. The final reaction in the sequence is catalyzed by tryptophan synthase. This enzyme has an a2/32 subunit structure and can be dissociated into two a subunits and a /32 subunit that catalyze different parts of the overall reaction ... 

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