Stereoselective analysis of endomorphin diastereomers: resolution of biologically active analogues by capillary electrophoresis applying cyclodextrins as mobile phase additives.
Seven diastereomer pairs of tetrapeptide analogues (TP) of endomorphin-1 and -2 were synthesized. A stereoselective capillary electrophoretic method was developed for controlling stereoisomeric ratio or purity. The isoelectric points of the tetrapeptides were between 8.3 and 8.9 as predicted and measured. A few of the analytes could be resolved without selectors due to the difference in their mobility. Neutral and anionic cyclodextrins (CDs) were applied in order to improve resolution. Stability constants as well as the mobilities of complexes were determined. Contributions of differences in the mobilities of free analytes and in the mobilities and stabilities of their complexes formed by CDs were equally important in the efficient resolution and migration order of diastereomers. As a result of the optimization of the pH of buffers and the concentration of the CD derivatives each diastereomer pair was resolved at baseline at least or better.
Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1525 Budapest, P.O.B.: 17, Hungary. nemeth.krisztina@ttk.mta.hu
Krisztina
K
Németh
Jayapal Reddy
JR
Mallareddy
Celesztina
C
Domonkos
Júlia
J
Visy
Géza
G
Tóth
Antal
A
Péter
D002021:Buffers; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary; D006863:Hydrogen-Ion Concentration; D007526:Isoelectric Point; D008956:Models, Chemical; D009842:Oligopeptides / Q000032:analysis* / Q000138:chemical synthesis; D013237:Stereoisomerism
D002021:Buffers; D003505:Cyclodextrins; D009842:Oligopeptides; C105293:endomorphin 1; C105294:endomorphin 2