PEPTIDE-SYNTHESIS AIMING AT ELUCIDATION AND CREATION OF PROTEIN FUNCTIONS

The recent development of molecular biology has been elucidating outli nes of the cross-talk of biomolecules. The understanding of the functi on of these biomolecules from the viewpoint of chemistry is now demand ed not only for the understanding of biological systems but also for t he creation of novel functional molecules. Here two topics are describ ed about peptide synthesis aiming at the elucidation and the creation of protein functions. The first topic is the development of approaches for the synthesis of Tyr (SO3H)-containing peptides. Tyrosine sulfati on is one of the most popular protein post-translational modifications . Synthetic peptides are of great help for the elucidation of the biol ogical significance of tyrosine sulfation. We have developed two appro aches for the efficient synthesis of tyrosine sulfate [Tyr (SO3H)]-con taining peptides. The first approach employs a dimethylformamide sulfu r trioxide (DMF-SO3) complex as a sulfating agent and safety-catch pro tecting groups for the selective sulfation of tyrosine in the presence of serine. The second approach employs the direct introduction of Tyr (SO3H) into the peptide chain in the form of Fmoc-Tyr(SO3Na) followed by deprotection at 4 degrees C in trifluoroacetic acid. These approach es were successfully applied for the synthesis of cholecystokinin (CCK )-related peptides. The second topic deals with new approaches for the creation of artificial proteins through assembling alpha-helical pept ides via selective disulfide or thioether formation. Approaches to ass emble individual peptide segments on a peptide template were also deve loped. Four peptides corresponding to the transmembrane segments of th e sodium channel (S4 in repeat I-IV) were assembled on a peptide templ ate to give a protein having ion channel activity with rectification.