Towards identifying preferred interaction partners of fluorinated amino acids within the hydrophobic environment of a dimeric coiled coil peptide.

Phage display technology has been applied to screen for preferred interaction partners of fluoroalkyl-substituted amino acids from the pool of the 20 canonical amino acids. A parallel, heterodimeric alpha-helical coiled coil was designed such that one peptide strand contained one of three different fluorinated amino acids within the hydrophobic core. The direct interaction partners within the second strand of the dimer were randomized and coiled coil pairing selectivity was used as a parameter to screen for the best binding partners within the peptide library. It was found that despite their different structures, polarities and fluorine contents, the three non-natural amino acids used in this study prefer the same interaction partners as the canonical, hydrophobic amino acids. The same technology can be used to study any kind of non-canonical amino acids. The emerging results will provide the basis not only for a profound understanding of the properties of these building blocks, but also for the de novo design of proteins with superior properties and new functions.

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