Biosynthesis and biological screening of a genetically encoded library based on the cyclotide MCoTI-I.

Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
ChemBioChem (Impact Factor: 3.06). 09/2009; 10(16):2663-70. DOI: 10.1002/cbic.200900534
Source: PubMed
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    ABSTRACT: The discovery of inteins in the early 1990's opened the door to a wide variety of new technologies. Early engineered inteins from various sources allowed the development of self-cleaving affinity tags and new methods for joining protein segments through expressed protein ligation. Some applications were developed around native and engineered split inteins, which allow protein segments expressed separately to be spliced together in vitro. More recently, these early applications have been expanded and optimized through the discovery of highly efficient trans-splicing and trans-cleaving inteins. These new inteins have enabled a wide variety of applications in metabolic engineering, protein labeling, biomaterials construction, protein cyclization and protein purification.
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    ABSTRACT: Cyclotides are a family of naturally occurring backbone-cyclized macrocyclic mini-proteins from plants that have a knotted trio of intramolecular disulfide bonds. Their structural features imbue cyclotides with extraordinary stability against degradation at elevated temperatures or in the presence of proteolytic enzymes. The plasticity of their intra-cysteine loop sequences is exemplified by the more than 250 natural cyclotides sequenced to date, and this tolerance to sequence variation, along with their diverse bioactivities, underpins the suitability of the cyclic cystine knot (CCK) motif as a valuable drug design scaffold and research tool for protein engineering studies. Here we review the recent literature on applications of cyclotides for the stabilization of peptide epitopes and related protein engineering studies. Possible future directions in this field are also described. © 2013 Wiley Periodicals, Inc. Biopolymers, 2013.
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