PRODUCTION SYNTHESIS OF INSULIN-LIKE GROWTH FACTOR II

NEW METHODS ARE NEEDED THAT WILL ALLOW FOR THE ROUTINE PRODUCTION BY SOLID-PHASE SYNTHESIS OF PEPTIDES OF 60 TO 70 AMINO ACIDS IN LENGTH ON THE 50- TO 100-GRAM SCALE. CURRENTLY, PEPTIDES CAN BE MADE EITHER BY SOLID-PHASE SYNTHESIS TECHNIQUES ON A SMALL SCALE (UP TO 5 GRAMS) OR BY GENETIC ENGINEERING; BOTH OF THESE PRODUCTION METHODS ARE COSTLY AND RESULT IN VERY HIGH PRICES FOR COMMERCIALLY AVAILABLE PEPTIDES. THIS PROJECT WILL DEVELOP THE REQUIRED TECHNIQUES FOR THE SOLID-PHASE SYNTHESIS OF INSULIN-LIKE GROWTH FACTOR II (IGF-II) BY FRAGMENT ASSEMBLY AND WILL PRODUCE 50 TO 100 GRAMS OF THIS PEPTIDE BY THE END OF PHASE II. THE TECHNIQUES DEVELOPED FOR THE SYNTHESIS OF THIS PEPTIDE GROWTH FACTOR, WHICH IS 67 AMINO ACIDS IN LENGTH AND CONTAINS THREE INTRACHAIN DISULFIDES, WILL ALSO BE DIRECTLY APPLICABLE TO OTHER BIOLOGICALLY ACTIVE PEPTIDES, SUCH AS EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF-ALPHA). ONLY BY DEVELOPING NEW METHODS ANDAPPROACHES CAN PEPTIDES OF LONGER LENGTH AND GREATER STRUCTURAL COMPLEXITY BE ROUTINELY PRODUCED COMMERCIALLY AT REASONABLE COSTS. THIS PROJECT WILL USE A NEW ACID-SENSITIVE SOLID-PHASE SUPPORT RESIN TO BUILD THE REQUIRED PROTECTED FRAGMENTS BY FMOC SOLID-PHASE PEPTIDE SYNTHESIS. PHASE I WILL FOCUS ON THE SMALL-SCALE PRODUCTION OF IGF-II BY FRAGMENT ASSEMBLY.