Synthesis and purification of peptides

• Main Author: Irving, Stephen L.
• Published: University of Edinburgh 1994
• Subjects: 547.7
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.652848

Improved routes to tetrabenz[<I>a,c,g,i</I>]fluorene derivatives have been developed, allowing the synthesis of N<SUP>α</SUP>-17-tetrabenzo[<I>a,c,g,i</I>]fluorenyl-methoxycarbonyl (tbfmoc) urethane derivatives of alanine, leucine, isoleucine, methionine and valine. The chloroformate and pentafluorophenyl carbonate of 17-tetrabenzo[<I>a,c,g,</I>]fluorenylmethanol have been prepared and used to introduce the base-labile Tbrmoc group onto the N<SUP>α</SUP>-termini of resin-bound peptides. The high affinity of the Tbrmoc group for porous graphitised carbon (PGC) has been exploited for the purification of a range of synthetic peptides (23-85 residues). A comparison of various basic solvent systems used to elute the purified peptide from PGC is presented. The hydrophobicity of the Tbfmoc group has been used to simplify the purification of a ubiquitin analogue, UbY59F (76 residues), by the enhanced retention of the Tbfmoc peptide on RP-HPLC. A new synthesis of 2-hydroxydibenzocycloheptadien-5-one has been advised. This compound has been used to develop acid-labile linkers for the synthesis of peptide C-terminal alkyl amides and aza-glycine peptides, compatible with the Fmoc/<SUP>t</SUP>Bu solid phase method. Alternative modes of attachment of the linker to polystyrene resin are compared for the synthesis of bombesin, a peptide amide.