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Solid phase synthesis and NMR conformational studies on cyclic decapeptide template molecule

✍ Scribed by Zheng-Hong Peng


Publisher
Wiley (John Wiley & Sons)
Year
1999
Tongue
English
Weight
152 KB
Volume
49
Category
Article
ISSN
0006-3525

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✦ Synopsis


Selectively addressable topological templates represent a key feature in the de novo design of proteins using the TASP concept (Template Assembled Synthetic Proteins). The regioselectively addressable (orthogonally protected) lysine-containing cyclic templates are especially interesting for combinatorial chemistry. We report the synthesis and structural analysis of a series of cyclic and bicyclic decapeptide templates (model of TASP molecules). The peptides were synthesized via solid phase synthesis and followed by solution cyclization. The conformation of the peptides was studied by proton nmr spectroscopy in dimethylsulfoxide and in trifluoroethanol/water. The structure of the peptide template was calculated with the program DIANA and followed by simulated annealing from the nmr experimental constraints. The peptide adopts a fold comprising two ␤-strands and two type II ␤-turns predicted for conformationally well-defined templates. The design of such a restained cyclic decapeptide template will be discussed along with Regioselectively Addressable Functionalized Template (RAFT) molecular recognition and template for combinatorial synthesis.