Combined Solid Phase and Solution Synthesis of the Fully Protected Segment 74-99 of HIV 1-Protease with the Application of a New Trityl-Linker

B ernd H enkel, Lianshan Zhang, Carsten G oldam m er, Ernst Bayer* Institute of Organic Chemistry, University of Tübingen, Auf der Morgenstelle 18, D-72076 Tübingen, Germany Z. Naturforsch. 51b, 1339-1346 (1996); received April 10, 1996 HIV 1-Protease, Trityl-Linker, Fragment Condensation, Peptide Synthesis, Ionspray-MS, Chiral Gas-chromatography A new trityl-linker for the strategy of combined solid phase and solution synthesis has been used for the synthesis of the fully protected segment 74-99 of HIV 1-protease. The fully protected fragments 74-81, 82-99 and 90-99 have been synthesized on the polystyrenepolyethylenglykol resin TentaGel, split off with dilute acetic acid and assembled in solution without loss of side-chain protecting groups. After protection of the C-terminus of the frag­ ment 90-99, the second fragment was coupled with TBTU/NMM. The couplings were moni­ tored by IS-MS and HPLC. Racemization was checked by chiral gas-chromatography on a Chirasil-Val capillary.