Influence of solid support, solvent and coupling reagent on the head-to-tail cyclization of resin-bound peptides.
Head-to-tail cyclization of peptides attached to insoluble supports by means of the side chains of aspartic acid or glutamic acid allows the rapid synthesis of cyclic peptides of widely varied amino acid sequence. However, two side reactions dramatically reduce the yield of the desired compound; these are (1) interpeptide condensation that creates dimers, trimers and higher-order oligomers and (2) racemization of the C-terminal residue. A comparison was made between benzotriazoyloxy-tris-(dimethyl-amino)phosphonium hexafluorophosphate (BOP) and diisopropylcarbodiimide (DIPCDI) as cyclization reagents on kieselguhr-supported polydimethylacrylamide, chloromethyl-PolyHipe, and two commercially available polystyrene supports using DMF, CH2Cl2 and THF as cyclization solvents. Both of the side reactions are dependent on the amino acid sequence, the reagent used to couple the ends of the peptide and the solid support.
McMurray
J S
JS
University of Texas M.D. Anderson Cancer Center, Houston.
Lewis
C A
CA
Obeyesekere
N U
NU
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D002234:Carbodiimides / Q000737:chemistry; D004952:Esters / Q000138:chemical synthesis; D005449:Fluorenes / Q000737:chemistry; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D009943:Organophosphorus Compounds; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D012116:Resins, Plant; D012997:Solvents; D013237:Stereoisomerism
D000596:Amino Acids; D002234:Carbodiimides; D004952:Esters; D005449:Fluorenes; D007202:Indicators and Reagents; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009943:Organophosphorus Compounds; D010456:Peptides, Cyclic; D012116:Resins, Plant; D012997:Solvents; C031032:benzotriazol-1-yloxy-tris(dimethylamino)phosphonium; C081611:1,3-diisopropylcarbodiimide