The search for new and effective chiral selectors capable of separating a wide variety of enantiomeric compounds is an ongoing process. In the past decade, macrocyclic antibiotics have proved to be an exceptionally useful class of chiral selectors for the separation of enantiomers of biological and pharmacological importance by means of HPLC, TLC and electrophoresis. More chiral analytes have been resolved through the use of glycopeptides than with all the other macrocyclic antibiotics combined (ansamycins, thiostrepton, aminoglycosides, etc.). The glycopeptides avoparcin, teicoplanin, ristocetin A and vancomycin have been extensively used as chiral selectors in the form of chiral bonded phases in HPLC, and HPLC stationary phases based on these glycopeptides have been commercialized. Teicoplanin, vancomycin, their analogs and ristocetin A seem to be the most useful glycopeptide HPLC bonded phases for the enantioseparation of proteins and unusal native and derivatized amino acids. In fact, the macrocyclic glycopeptides are to some extent complementary to one another: where partial enantioresolution is obtained with one glycopeptide, there is a high probability that baseline or better separation can be obtained with another. This review sets out to characterize the physicochemical properties of these antibiotics and their application in the enantioseparations of amino acids. The mechanism of separation, the sequence of elution of the stereoisomers and the relation to the absolute configuration are also discussed.

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Endomorphins were subjected to a number of structural modifications in a search for their bioactive conformations. The alicyclic β-amino acids cis-(1S,2R)ACPC/ACHC, cis-(1R,2S)ACPC/ACHC, trans-(1S,2S)ACPC/ACHC, and trans-(1R,2R)ACPC/ACHC were introduced into endomorphins to examine the conformational effects on the bioactivity. Use of a combination of receptor binding techniques, 1 H NMR, and molecular modeling allowed the conclusion that Pro 2 substitution by these residues causes changes in structure, proteolytic stability, and pharmacological activity. It seems that the size of the alicyclic β-amino acids does not have marked influence on the receptor binding affinities and/or selectivities. Among the new analogues, the cis-(1S,2R)ACPC 2 and cis-(1S,2R)ACHC 2 -containing derivatives displayed the highest binding potencies and efficacies in receptor binding and ligand-stimulated [ 35 S]GTPγS functional experiments. Molecular dynamic simulations and 1 H NMR studies of the cis-ACPC/ACHC-containing analogues revealed that many conformations are accessible, though it is most likely that these peptides bind to the µ-opioid receptor in a compact, folded structure rather than extended.