PREPARATION OF THE VERY ACID-SENSITIVE FMOC-LYS(MTT)-OH - APPLICATIONIN THE SYNTHESIS OF SIDE-CHAIN TO SIDE-CHAIN CYCLIC-PEPTIDES AND OLIGOLYSINE CORES SUITABLE FOR THE SOLID-PHASE ASSEMBLY OF MAPS AND TASPS

ylmethoxycarbonyl-N-epsilon-4-methyltrityl-lysine, [Fmoc-Lys(Mtt)-OH], was prepared in two steps from lysine, in 42% overall yield. The N-ep silon-Mtt function can be quantitatively removed upon treatment with 1 % TFA in dichloromethane or with a 1:2:7 mixture of acetic acid/triflu oroethanol/dichloromethane for 30 min and 1 h at room temperature, res pectively. Under these conditions, groups of the tert-butyl type and p eptide ester bonds to TFA-labile resins, such as the 2-chlorodiphenylm ethyl- and the Wang-resin, remained intact. The utility of the new der ivative in peptide synthesis has been exemplified with the synthesis o f a cyclic cholecystokinin analog. As an example of further applicatio n, five types of lysine cores suitable for the solid-phase synthesis o f one, two or three epitopes containing antigenic peptides or template -assembled synthetic proteins have been synthesized on Merrifield, Wan g and 2-chlorodiphenylmethyl resin. (C) Munksgaard 1995.