Collect. Czech. Chem. Commun. 1989, 54, 2271-2275

Preparation and characterization of new analogues of Dalargin

Jan Pospíšeka, Tomislav Bartha, Zhanna D. Bespalovab, Mikhail I. Titovb, Hana P. Maškováa, Alexander S. Molokoedovb and Nikolai F. Sepetovb

a Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6, Czechoslovakia
b Institute of Experimental Cardiology, Cardiology Research Center of the U.S.S.R., Academy of Medical Sciences, 121552 Moscow, U.S.S.R.


Tert-butyloxycarbonyl-O-tert-butyloxycarbonyl-L-tyrosyl-D-alanyl-glycyl-L-phenylalanyl-DL-neopentylglycyl-L-arginine was prepared by means of fragment condensation in solution. Protecting groups were removed with trifluoroacetic acid and the diastereoisomeric peptides were separated employing high-performance liquid chromatography (HPLC) and the absolute configuration of neopentylglycine in each diastereomer was determined by two different methods: analysis of enzymatic degradation with carboxypeptidase B and 1H NMR spectroscopic data. The hexapeptide with L-neopentylglycine in position 5 exhibited a 20 times higher activity in a standard test on isolated guinea-pig ileum (GPI). The hexapeptide with D-neopentylglycine in position 5 exhibited a 4 times higher activity than Dalargin in the GPI test but its effect was prolonged in comparison to the analog with L-neopentylglycine and Dalargin.