Synthesis of the proteinase inhibitor LEKTI domain 6 by the fragment condensation method and regioselective disulfide bond formation.
Proteinase inhibitors are of high pharmaceutical interest and are drug candidates for a variety of indications. Specific kallikrein inhibitors are important for their antitumor activity and their potential application to the treatment of skin diseases. In this study we describe the synthesis of domain 6 of the kallikrein inhibitor Lympho-Epithilial Kazal-Type Inhibitor (LEKTI) by the fragment condensation method and site-directed cystine bridge formation. To obtain the linear LEKTI precursor, the condensation was best performed in solution, coupling the protected fragment 1-22 to 23-68. This method yielded LEKTI domain 6 of high purity and equipotent to the recombinantly produced peptide.
Vasileiou
Zoe
Z
Department of Chemistry, University of Patras, Patras, Greece.
Barlos
Kostas K
KK
Gatos
Dimitrios
D
Adermann
Knut
K
Deraison
Celine
C
Barlos
Kleomenis
K
D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D015843:Serpins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000235:genetics
D004220:Disulfides; D010446:Peptide Fragments; D015843:Serpins