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Synthesis of Lipidated eNOS Peptides by Combining Enzymatic, Noble Metal‐ and Acid‐Mediated Protecting Group Techniques with Solid Phase Peptide Synthesis and Fragment Condensation in Solution
Author(s) -
Machauer Rainer,
Waldmann Herbert
Publication year - 2001
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20010702)7:13<2940::aid-chem2940>3.0.co;2-u
Subject(s) - redox , ultramicroelectrode , diffusion , chemistry , diffusion layer , electrosynthesis , catalysis , electrode , analytical chemistry (journal) , damköhler numbers , kinetics , nernst equation , electrochemistry , halide , inorganic chemistry , chemical physics , thermodynamics , chromatography , cyclic voltammetry , organic chemistry , physics , quantum mechanics , combustion
Lipid‐modified proteins play decisive roles in important biological processes such as signal transduction, organization of the cytoskeleton, and vesicular transport. Lipidated peptides embodying the characteristic partial structures of their parent lipidated proteins and semisynthetic proteins synthesized from such peptides are valuable tools for the study of these biological phenomena. We have developed an efficient synthesis strategy that allows for the synthesis of long multiply lipidated peptides embodying various side chain functional groups. The strategy was successfully applied in the synthesis of the N‐terminal undetrigintapeptide of endothelial NO‐synthase and related lipopeptides. Key elements of the synthesis strategy are the combined use of the enzyme‐labile para ‐phenylacetoxybenzyloxycarbonyl (PhAcOZ) urethane as N‐terminal blocking group, the Pd 0 ‐sensitive allyl ester as C‐terminal protecting function and acid‐labile side chain protecting groups for solution‐phase synthesis of labile S ‐palmitoylated building blocks under the mildest conditions with solid‐phase techniques and solution‐phase fragment condensations. The successful synthesis of the triply lipidated 29‐mer eNOS peptide convincingly demonstrates the full capacity of the protecting group methods.