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The design, synthesis, and crystallization of an alpha‐helical peptide
Author(s) -
Eisenberg David,
Wilcox William,
Eshita Steven M.,
Pryciak Peter M.,
Ho Siew Peng,
Degrado William F.
Publication year - 1986
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340010105
Subject(s) - tetramer , antiparallel (mathematics) , crystallography , amphiphile , chemistry , folding (dsp implementation) , peptide , crystallization , circular dichroism , stereochemistry , side chain , helix (gastropod) , protein design , protein structure , copolymer , physics , organic chemistry , biochemistry , quantum mechanics , magnetic field , electrical engineering , enzyme , engineering , polymer , ecology , snail , biology
Twelve‐ and sixteen‐residue peptides have been designed to form tetrameric alphahelical bundles. Both peptides are capable of folding into amphiphilic alpha‐helices, with leucyl residues along one face and glutamyl and lysyl residues along the opposite face. Four such amphiphilic alpha‐helices are capable of forming a noncovalently bonded tetramer. Neighboring helices run in antiparallel directions in the design, so that the complex has 222 symmetry. In the designed tetramer, the leucyl side chains interdigitate in the center in a hydrophobic interaction, and charged side chains are exposed to the solvent. The designed 12‐mer(ALPHA‐1) has been synthesized, and it forms helical aggregates in aqueous solution as judged by circular dichroic spectroscopy. It has also been crystallized and characterized by x‐ray diffraction. The crystal symmetry is compatible with (but does not prove) the design. The design can be extended to a four‐alpha‐helical bundle formed from a single polypeptide by adding three peptide linkers.