Facilitated synthesis of peptaibols: alamethicin via enzymatic segment condensation.
We have used a combined chemical-enzymatic approach to facilitate the total synthesis of the 20-residue peptaibol, alamethicin. The 1-11 segment of alamethicin, having a C-terminal Gly, and the 12-20 segment, having an N-terminal Leu, were prepared by well-established chemical methods, and then coupled using papain to afford a 54% yield of alamethicin in straightforward fashion. In contrast to the reported chemical syntheses of alamethicin requiring side-chain protection at Glu,18 the papain-catalyzed coupling proceeded readily and selectively using a C-terminal segment having a free gamma-carboxyl group at this position. Several alamethicin partial sequences were obtained via enzymatic formation of the Gly11-Leu12 bond. The high efficiency of this route is illustrated by the enzymatic assembly of the 1-17 alamethicin fragment on a 400-mg scale in 62% yield. An alternative route to alamethicin through enzymatic formation of the Ala6-Gln7 bond was less successful because of a low yield in the final coupling.
Slomczynska
U
U
Institute of Organic Chemistry, Politechnika, Lodz, Poland.
Zabrocki
J
J
Kaczmarek
K
K
Leplawy
M T
MT
Beusen
D D
DD
Marshall
G R
GR
D000408:Alamethicin / Q000138:chemical synthesis*; D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*
D010455:Peptides; D000408:Alamethicin