Polymer-supported approach for solution-phase synthesis of cysteine trap protease inhibitors: procedure for straightforward optimization of the P1-P1' pocket.
Peptide-based reversible and irreversible cysteine proteases inhibitors are well reported in the literature. Many of these compounds have an electrophilic carbonyl group as a cysteine trap in the place of a scissile amide moiety of the natural substrate. As a common mechanism strategy, we have designed a probe library of a cysteine trap for rapid optimization of P1-P1' pockets of different cysteine proteases. The synthesis of this library using a straightforward methodology based on polymer-supported reagents and scavengers to avoid tedious purification steps has been achieved. For the selective monobromination of diazo ketones, preparation of a new supported reagent, piperidinoaminomethylpolystyrene hydrobromide, is also described.
Yadav-Bhatnagar
Neerja
N
Automated Synthesis & New Technologies, Aventis Pharma, 102 Route de Noisy, F-93325 Romainville Cedex, France. neerja.bhatnagar@aventis.com
Desjonquères
Nicolas
N
Mauger
Jacques
J
D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D003979:Diazonium Compounds / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D018716:Molecular Mimicry; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000737:chemistry
D015853:Cysteine Proteinase Inhibitors; D003979:Diazonium Compounds; D015335:Molecular Probes; D009842:Oligopeptides; D011108:Polymers