Progress in the preparation of peptide aldehydes via polymer supported IBX oxidation and scavenging by threonyl resin.
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.
Sorg
Gerhard
G
Institute of Organic Chemistry, University of Tübingen, Tübingen, Germany.
Thern
Bernd
B
Mader
Oliver
O
Rademann
Jörg
J
Jung
Günther
G
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*
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