SYNTHESIS OF THE 3-REPEAT REGION OF HUMAN TAU-2 BY THE SOLID-PHASE ASSEMBLY OF BACKBONE AMIDE-PROTECTED SEGMENTS

The synthesis, purification, and use of N-(2-acetoxy-4-methoxybenzyl)( AcHmb) backbone amide protected segments in the preparation of Asp(158 )-Leu(251) from the 3-repeat region of human tau-2 has been investigat ed. Fmoc/tert-butyl based(1,2) fully protected segments of 9-21 residu es, containing appropriately placed AcHmb protection were prepared on Polyhipe SU500 resin through a 2-chlorotrityl linker. Protected segmen ts, cleaved with 0.75% trifluoroacetic acid in dichloromethane, were e asily purified in 100s of milligram quantities by either silica gel ch romatography or standard aqueous acetonitrile based reverse phase prep arative HPLC. Purified protected segments, typically soluble at >500 m g mL(-1) in dimethylformamide, coupled efficiently and economically to a growing resin-bound assembly, to give the 94-mer human tau-2 with a n overall purified yield of 2.50 mu mol (16.7%).