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Facilitated synthesis of peptaibols: Alamethicin via enzymatic segment condensation
Author(s) -
Slomczynska Urszula,
Zabrocki Janusz,
Kaczmarek Krzysztof,
Leplawy Miroslaw T.,
Beusen Demise D.,
Marshall Garland R.
Publication year - 1992
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360321106
Subject(s) - alamethicin , chemistry , enzyme , biochemistry , membrane , lipid bilayer
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 γ‐carboxyl group at this position. Several alamethicin partial sequences were obtained via enzymatic formation of the Gly 11 −Leu 12 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 Ala 6 −Gln 7 bond was less successful because of a low yield in the final coupling. © 1992 John Wiley & Sons, Inc.