| abstract |
This invention relates generally to cyclic polypeptides comprising a thioether linkage and methods for their preparation. More particularly, this invention relates to halogenated polypeptides having at least one haloalanine-like amino acid, and methods for their preparation which involve converting the hydroxyl group (i.e., -OH) of a serine-like amino acid to a halo group (i.e., -X where X is Cl, Br, or I) with the aid of a phosphorus-based halogenation reagent such as a triphenylphosphine dihalide (i.e., (C6H5)3PX2, wherein X is Cl, Br, or I), a triphenylphosphite dihalide (i.e., (C6H5O)3PX2, wherein X is Cl, Br, or I), or a mixture of triphenylphosphine or triphenylphosphite with a halohydrocarbon (i.e., "halo-conversion"). This invention also relates to cyclic polypeptides having at least one polypeptide loop comprising a thioether linkage, and methods for their preparation which employ halogenated polypeptides and which involve intramolecular alkylation of the thiol group of a cysteine-like amino acid by the halo group of a haloalanine-like amino acid under suitable basic conditions to form a thioether linkage (i.e., "cyclization"). |