Peptides cyclodextrins

Scheme 6 Synthesis of Peptide-Cyclodextrin Conjugates1241. co2h...

Pean, C., Wijkhuisen, A., Djedaini-Pilard, P. etal. Pharmacological investigations of new peptide-cyclodextrins. In Proceedings of the 9th... 

Pean, C., Wijkhuisen, A., Djedaini-Pilard, F., et al. (1998) Pharmacological investigations of new peptide-cyclodextrins. In Torres Labandeira, J.J. and Vila-Jato, J.L. (eds). Proceedings of the 9th International Symposium on Cyclodextrins, pp. 387-390. Kluwer Academic Press, Dordrecht. 

Phenylthiocarbamoyl derivatives of 18 chiral amino acids were separated on a C8 column connected in series to a phenylcarbamoylated (3-cyclodextrin column (Iida et al., 1997). The Cg column separated the derivatized amino acids from one another entering the chiral column. Under this configuration several enantiomers of adjacent amino acids coeluted resulting in poor resolution. However, this configuration was successful in determining the amino acid sequence and chirality of the amino acids in a D-amino acid containing peptide. 

In a similar fashion, steroids are molecules that have been investigated by disruption of FRET. The sensor is a double labeled peptide with cyclodextrin bound to one side chain. The latter keeps the fluorophores closely together by accommodating the coumarin into its cavity thereby ensuring efficient FRET. Steroids compete for the cavity of cyclodextrin and displace the coumarin reducing FRET efficiency. This model, although useful for in vitro applications, seems to be poorly selective for its application in biological samples [95],... 

Hossain, M. A., Mihara, H. and Ueno, A. (2003). Novel peptides bearing pyrene and coumarin units with or without beta-cyclodextrin in their side chains exhibit intramolecular fluorescence resonance energy transfer. J. Am. Chem. Soc. 125, 11178-11179. 

As yet, the number of applications is limited but is likely to grow as instrumentation, mostly based on existing CE systems, and columns are improved and the theory of CEC develops. Current examples include mixtures of polyaromatic hydrocarbons, peptides, proteins, DNA fragments, pharmaceuticals and dyes. Chiral separations are possible using chiral stationary phases or by the addition of cyclodextrins to the buffer (p. 179). In theory, the very high efficiencies attainable in CEC mean high peak capacities and therefore the possibility of separating complex mixtures of hundreds of... 

Erythromycin, a macrolide antibiotic, lacks a significant chromophore. Detection sensitivity was enhanced by using a wavelength of 200 nm and selecting an injection solvent of lower conductivity than the BGE. In order to facilitate the separation of erythromycin and its related substances, 35% (v/v) ethanol was incorporated into a 150 mM phosphate buffer pH 7.5. Resolution of all of the compounds was achieved in approximately 45 min. The method was employed as an assay method for erythromycin and for impurity determination. Peptide antibiotics, such as colistin and polymyxin, are mixtures of many closely related compounds. A validated CZE method for impurity analysis of polymyxin B was described, employing 130 mM triethanolamine-phosphate buffer at pH 2.5 to reduce the adsorption of analyte onto the capillary wall. Methyl-/l-cyclodextrin (M-/1-CD) and 2-propanol were found to be necessary for selectivity enhancement. Using similar buffer additives, the same group developed and validated a method for colistin analysis. ... 

The properties of natural macrocycles, the cyclodextrins, has stimulated interest in the preparation of synthetic macrocycles. Three basic types have been made macrocyclic amines, cyclophanes, and cyclic peptides. Hersh-field and Bender (33) prepared a bicyclic amine with hydroxamate sub-... 

Three approaches can be employed to separate peptide stereoisomers and amino acid enantiomers separations on chiral columns, separations on achiral stationary phases with mobile phases containing chiral selectors, and precolumn derivatization with chiral agents [111]. Cyclodextrins are most often used for the preparation of chiral columns and as chiral selectors in mobile phases. Macrocyclic antibiotics have also been used as chiral selectors [126]. Very recently, Ilsz et al. [127] reviewed HPLC separation of small peptides and amino acids on macrocyclic antibiotic-based chiral stationary phases. 

Synthetic peptides containing side-chain modification have also been used as molecular scaffolds for the preparation of multiple receptors and molecular devices. 5 These include the use of crown ethers, cyclodextrins, porphyrins, and peptides with metal-binding sites (including ferrocenyl and EDTA side chains) (Section 9.4). Cyclization procedures have been developed to prepare biologically active cycloisodityrosine peptides which contain 14-or 17-membered rings (Section 9.5). The use of tryptathionine, a cross-linking dipeptide consisting of side-chain-to-side-chain linked L-Trp-L-Cys that is present in phallotoxins, 6 a family of cyclic heptapeptides, is also described (Section 9.6). 

Scheme 7 Coupling of Peptide Segments on a Cyclodextrin Derivative 251...

The separation of enantiomers can be effected either by transforming them into diastereoisomers using a chiral reagent and separating them on conventional phases or by separating the enantiomers on chiral phases. The utilization of chiral phases has not yet become routine, but studies of enantiomeric dipeptides have been carried out (115,116). Pirkle et al. (117) and Hyun et al. (118) separated enantiomeric di- and tripeptides (methyl esters of /V-3-5-dinitrobenzoyl derivatives) on chiral stationary phases (CSPs) derived from (R)-a-arylalkylamines, (S)-N-(2-naphthyl) valine, or (S)-1 -(6,7-dimethyl-1 -naphthyl) isobutylamine. These workers were able to separate four peaks for each dipeptide derivative, corresponding to the two enantiomeric pairs (R,R)/(S,S) and (R,S)/(S,R). Cyclodextrin-bonded stationary phases and chiral stationary immobilized a-chymotrypsin phases were used to separate enantiomeric peptides (118a,b). 

Recently, a modified /J-cyclodextrin was also used as a scaffold in the preparation of a structure that has seven -sheet-forming peptides (45) [38]. Although no structural analysis was reported, this represents the first synthesis of a peptidic architecture with seven adjacent peptide units. 

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