R. Gothe, L. Seyfarth, C. Schumann
May 1, 1999
Citations
0
Influential Citations
11
Citations
Journal
Journal Fur Praktische Chemie-chemiker-zeitung
Abstract
Analogues of both the nonapeptides, bradykinin and bradykinin potentiating nonapeptide BPP9α, were synthesized using HYCRAMTM-technique. The bradykinin analogues were assembled by the Boc-, Ddz- and Fmoc-strategy starting with Boc-Arg(Aloc)2-OCr–OH, Ddz-Arg(Mtr)-OCr–OH and Fmoc–Arg(Mtr)-OCr–OH. While Boc- and Ddz-strategy provide peptides in good yield and purity, the Fmoc-strategy leads to a loss of peptide from resin. For simultaneous cleavage from HYCRAMTM-resin and removal of Aloc-side chain protection optimized conditions for catalytic cleavage with Pd° were developed. As shown by the synthesis of BPP9αanalogues the HYCRAMTM-linker and the chlorotrityl resin allow the assembly of peptides with the C-terminal sequence Pro-Pro by preventing dioxopiperazine formation. Since the BPP9α sequence contains the tripeptide Trp-X-Arg an intramolecular migration of the NG-protecting group to the indole ring under conditions used for its removal had to be avoided. By the use of HYCRAMTM-linker in combination with Aloc protection for the guanidino group and Ddz for Nαno modification of Trp occurred. HYCRAMTM-technology in combination with Boc-, Ddz- or Aloc/All-protecting groups facilitates the synthesis of peptides with such very labile amino acids like cis-4-hydroxyproline.