title: Progress in the preparation of peptide aldehydes via polymer supported IBX oxidation and scavenging by threonyl resin.
abstract: Peptide aldehydes are of interest due to their inhibitory properties toward numerous classes of proteolytic enzymes such as caspases or the proteasome. A novel access to peptide aldehydes is described using a combination of solid phase peptide synthesis with polymer-assisted solution phase synthesis based on the oxidation of peptide alcohols with a mild and selective polymer-bound IBX derivative. The oxidation is followed by selective purification via scavenging the peptide aldehyde in a capture-release procedure using threonine attached to an aminomethyl resin. Peptide aldehydes are obtained in excellent purity and satisfying yield. The optical integrity of the C-terminal residue is conserved in a high degree. The procedures are compatible with the use of common side-chain protecting groups. The potential for using the method in parallel approaches is very advantageous. A small collection of new and known peptide aldehydes has been tested for inhibitory activity against caspases 1 and 3.
authors.affiliation: Institute of Organic Chemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Sorg
authors.forename: Bernd
authors.initials: B
authors.lastname: Thern
authors.forename: Oliver
authors.initials: O
authors.lastname: Mader
authors.forename: Jörg
authors.initials: J
authors.lastname: Rademann
authors.forename: Günther
authors.initials: G
authors.lastname: Jung
mesh_terms: D000438:Alcohols / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005449:Fluorenes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D012117:Resins, Synthetic / Q000737:chemistry*; D013912:Threonine / Q000737:chemistry*
chemical_list: D000438:Alcohols; D000447:Aldehydes; D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D061945:Caspase Inhibitors; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D012117:Resins, Synthetic; D013912:Threonine; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1