Synthesis of cyclic penta- and hexapeptides: a general synthetic strategy on DAS resin.
The active part or receptor-binding sequence of peptide hormones can usually be defined by a span of 4-8 amino acids. Cyclic penta- and hexapeptides are excellent model systems for performing conformational and structure-function studies on this class of bioactive molecules. A synthetic scheme has been devised comprising solid-phase Fmoc chemistry followed by resin cleavage, cyclization in solution, and, finally, side-chain deprotection. A new resin, DAS, cleaved under weak acid conditions, is an excellent solid-phase synthesis support, and HBTU or PyBOP are the activation reagents of choice, not only during synthesis, but also for the cyclization reaction. Three cyclic peptides were synthesized using this method, one requiring extensive side-chain protection, and this method has general applicability for any cyclic pentapeptide or hexapeptide, giving good yields and high purity.
Sowemimo
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V
Victorian College of Pharmacy, Monash University, Parkville, Australia.
Scanlon
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D
Jones
P
P
Craik
D J
DJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D012116:Resins, Plant
D000596:Amino Acids; C090352:DAS resin; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; D010456:Peptides, Cyclic; D012116:Resins, Plant; C073361:cyclo(Gln-Trp-Phe-Gly-Leu-Met); C072247:cyclo(Trp-Asp-Pro-Val-Leu)