Peptides chiral sensitivity

THE DISTINCT CHIRAL SENSITIVITY OF N-METHYLAMINO ACID RESIDUES AND SENSITIVITY TO ACID OF ADJACENT PEPTIDE BONDS... 

In order to improve selectivity and sensitivity, for those peptides that do not contain natural chromophores or flnorophores, pre- or postcolumn derivatization is nsnally applied. Roller and Eckert [129] presented a comprehensive review of derivatization methods snitable for the chromatography of peptides. A derivatization step can be also introduced in order to rednce the hydro-philicity of the analytes to enable RP-HPLC or to label racemic componnds by a chiral reagent to separate them as their diasteromers [129]. 

Fortunately, CD spectroscopy is sensitive not only to the local chirality of the peptide unit, but it also reflects global chirality, that is, the way the chiral units are arranged in space. Therefore, CD can detect different secondary structures within the polypeptide chain. There are four main classes of secondary structures for proteins the a helix, the p sheet, the p turn, and the random coil. In addition, there are also other helix and turn variants which will be discussed. 

In the absence of base, active esters of both N-alkoxycarbonyl amino acids and N -protected peptides undergo anninolysis with preservation of chiral integrity. There is ample evidence to substantiate this statementP d and no evidence to the contrary. But there is a wealth of accumulated evidence that active esters undergo isomerization when left in the presence of tertiary annine.t In this regard, 4-nitrophenyl esters are much more sensitive than trichlorophenyl esters and piperidino esters are exceptions in that they are unaffected by tertiary anoine.W The isomerization recently observed in the TBTU-mediated couplings of Fmoc-Cys(R )-OH in the presence of 1,2,3-benzotriazol-l-ol in continuous flow solid-phase synthesis is a further example of this phenomenon. The result can be attributed to the effect of tertiary amine on the benzotriazolyl ester that is formed by capture of the acyluronium intermediate before it has time to be aminolyzed. 

In order to obtain independent evidence for the involvement of the cyclodextrin cavity, fluorescence measurements were carried out for copper(II) ternary complexes with L- or D-tryptophan. In fact, the fluorescence spectrum of tryptophan has already been shown to be sensitive to the polarity of the microenvironment in which it is located and has been used in many studies as a probe for the conformation of proteins and peptides [53]. As for many fluorophores, the indole fluorescence of Trp is quenched by the copper(II) ion this effect has been used as a measure of the stability constants of copper(II) complexes [54, 55]. In a recent work, it has been shown that the fluorescence of dansyl derivatives of amino acids undergo enantioselective fluorescence quenching by chiral copper(n) complexes and that fluorescence measurements can be used for the study of enatioselectivity in the formation of ternary complexes in solution [56]. Bearing this in mind, we performed the same type of experiments by adding increasing amounts of the [Cu(CDhm)] + complex to a solution of D- or L-tryptophan [36]. The fluorescence titration curve shows that the artificial receptor inhibits the indole... 

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