Abstract: Electrochemical methods, preferably the Kolbe coupling reaction, are utilized to create intramolecularly bridged peptides, segments or peptide isosteres which are conformationally restricted and preferably, biologically active. Preferably, the peptide analogues contain methylene groups bridging particular amino acid side chains. Analogues of a variety of peptide hormones, including insulin, insulin-like growth factors, somatostatin, melanocyte stimulating hormone, and the like are prepared by the above methods. Such peptides are useful as agonists or antagonists for treatment of diseases associated with deficiency of the hormone or dysregulation of hormone activity, as well as for mechanistic studies to understand the interactions between peptide hormones and cells.

Abstract: A solid phase resin useful as a support for peptide synthesis is synthesized stepwise from a solid phase polymer by reacting a solid phase phenyl ether resin with an alkoxy benzoyl halide to form a solid phase having (alkoxybenzoyl)phenoxymethyl groups bound thereto. The hydroxy group of the benzoyl moiety may be converted to a free amine by reacting with an ammonium salt of a carboxylic acid and then hydrolyzing with alkali. Novel resins produced by this method include those in which the solid phase phenyl ether resin is a resin having alkyl phenyl moieties linked to alkoxy phenyl groups by an ether linkage.