Process for preparing cardiodilatin fragments; highly purified cardiodilatin fragments and intermediate products for the preparation of same

Abstract

The invention relates to a process for the preparation of cardiodilatin fragments, to highly purified cardiodilatin fragments, and to appropriate intermediates for the preparation of said fragments. Furthermore, the invention relates to highly purified cardiodilatin fragments which are free of peptide impurities and exhibit a single migration peak in capillary electrophoresis, as well as to appropriate processes for the preparation of same.

1 - 20 . (canceled)  
     
     
         21 . A fragment of ANP (95-126) selected from the group consisting of: 
 (a) Boc-Thr(tBu)-Ala-Pro-Arg(Pbf)-Ser(tBu)-Leu-Arg(Pbf)-Arg(Pbf)-Ser(tBu)-Ser(tBu)-Cys(Acm)-Phe-Gly-Gly-OH (SEQ ID 6);    (b) Fmoc-Arg(Pbf)-Met-Asp(OtBu)-Arg(Pbf)-Ile-Gly-Ala-Gln(Trt)-Ser(tBu)-Gly-Leu-Gly-OH (SEQ ID 7);    (c) Fmoc-Cys(Trt)-Asn(Trt)-Ser(tBu)-Phe-Arg(Pbf)-Tyr(tBu)OH (SEQ ID 8);    (d) Fmoc-Cys(Trt)-Asn(Trt)-Ser(tBu)-Phe-Arg(Pbf)-Tyr(tBu)-OtBu (SEQ ID 8);    (e) H-Cys(Trt)-Asn(Trt)-Ser(tBu)-Phe-Arg(Pbf)-Tyr(tBu)-OtBu (SEQ ID 8);    (f) Fmoc-Arg(Pbf)-Met-Asp(Otbu)-Arg(Pbf)-Ile-Gly-Ala-Gln(Trt)-Ser(tBu)-Gly-Leu-Gly-Cys(Trt)-Asn(Trt)-Ser(tBu)-Phe-Arg(Pbf)-Tyr(tBu)-OtBu (SEQ ID 9); and    (g) H-Arg(Pbf)-Met-Asp(Otbu)-Arg(Pbf)-Ile-Gly-Ala-Gln(Trt)-Ser(tBu)-Gly-Leu-Gly-Cys(Trt)-Asn(Trt)-Ser(tBu)-Phe-Arg(Pbf)-Tyr(tBu)-OtBu (SEQ ID 9).    
     
     
         22 . A fragment of ANP (95-126) selected from the group consisting of: 
 (a) Boc-Thr(tBu)-Ala-Pro-Arg(Pbf)-Ser(tBu)-Leu-Arg(Pbf)-Arg(Pbf)-Ser(tBu)-Ser(tBu)-Cys(Acm)-Phe-Gly-Gly-Arg(Pbf)-Met-Asp(OtBu)-Arg(Pbf)-Ile-Gly-Ala-G In (Trt)-Ser(tBu)-Gly-Leu-Gly-Cys(Trt)-Asn(Trt)-Ser(tBu)-Phe-Arg(Pbf)-Tyr(tBu)-OtBu- (SEQ ID 10); and    (b) H-Thr-Ala-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-Cys(Acm)-Phe-Gly-Gly-Arg-Met-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH (SEQ ID 5).    
     
     
         23 . The fragment of  claim 22 , wherein such fragment is stable.