fluorine in peptide design and protein engineering推荐.pdf

MICROREVIEW DOI: 10.1002/ejoc.200500205 Fluorine in Peptide Design and Protein Engineering Christian Jäckel[a] and Beate Koksch*[a] Keywords: Fluorine / Protein engineering / Peptide design / Non-natural amino acids / Secondary structure The use of fluorine has become well established in the analy- versially discussed. The systematic investigation of the inter- sis of protein structure and function, e.g. in tools such as 19F action properties of fluoroalkyl groups in a native polypep- NMR spectroscopy. The application of the unique electronic tide environment broadens the scope of fluorinated amino properties of this element for the structural and chemical acids to the rational design of structural motifs and protein modification of peptides and proteins emerged as a promis- interfaces. ing approach. However, the influences of amino acid fluori- (© Wiley-VCH Verlag GmbH Co. KGaA, 69451 Weinheim, nation on side-chain interactions in proteins are still contro- Germany, 2005) Introduction alignment of the twenty canonical amino acids, is limited by profound factors such as weak metabolic stability, bad The key to controlling the biological functionality and bioavailability in vivo, and insufficient biological potency. therapeutic efficacy of peptide-based drugs is provided by These issues arise from the