PEPTIDE-SYNTHESIS ON CHITIN

The use of chitin as a support for solid-phase peptide synthesis is de scribed and illustrated by synthesis of four peptides, varying in leng th from 10 to 29 residues. Syntheses were performed in a continuous-fl ow peptide synthesizer, using Fmoc chemistry. A cleavable linker, thox yformamido]-2,4-dimethoxybenzyl]-phenoxyacetic acid, was attached to c hitosan at the desired substitution level, and the complex acetylated to yield a linker substituted chitin. The effects of temperature, solv ents and degree of linker substitution on the syntheses were studied. Acyl carrier peptide (ACP) synthesis studies indicated that temperatur e was the single most important parameter. Increasing the temperature of the synthesis from 20 to 55 degrees C resulted in an enormous impro vement of this synthesis, with about 90% of the crude product being th e correct peptide. Denaturing solvents, such as DMSO, could be used wi thout significant effect on the flow properties of the support. The sy nthesis of one peptide was mainly improved by lowering the degree of s ubstitution from 0.3 to 0.1 mmol/g, suggesting peptide aggregation was a problem in this case. The results of three syntheses on chitin were comparable with those obtained with a commonly used commercial suppor t. This work shows that, under appropriate conditions, chitin can be u tilized directly as a support for peptide synthesis. (C) Munksgaard 19 96.