Cyclic Peptides, A Chemical Genetics Tool for Biologists

Horswill, Alexander R.; Benkovic, Stephen J.

doi:10.4161/cc.4.4.1585

Cited by 44 publications

(23 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Toward this end, a method to generate libraries of cyclic peptides that employs circularly permuted inteins which self-catalyze the cyclization of a target peptide has been developed in Escherichia coli (16)(17)(18)(19)(20)(21)(22). This method, termed split intein catalyzed ligation of proteins and peptides (SICLOPPS), has been previously used to select inhibitors of hydrolases, methyl transferases, and other proteins (17,20,(22)(23)(24).…”

mentioning

confidence: 99%

Evolution of cyclic peptide protease inhibitors

Young

Ahmad

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

122

127

View full text Add to dashboard Cite

We report a bacterial system for the evolution of cyclic peptides that makes use of an expanded set of amino acid building blocks. Orthogonal aminoacyl-tRNA synthetase/tRNA CUA pairs, together with a split intein system were used to biosynthesize a library of ribosomal peptides containing amino acids with unique structures and reactivities. This peptide library was subsequently used to evolve an inhibitor of HIV protease using a selection based on cellular viability. Two of three cyclic peptides isolated after two rounds of selection contained the keto amino acid p -benzoylphenylalanine ( p BzF). The most potent peptide (G12: GIXVSL; X = p BzF) inhibited HIV protease through the formation of a covalent Schiff base adduct of the p BzF residue with the ϵ-amino group of Lys 14 on the protease. This result suggests that an expanded genetic code can confer an evolutionary advantage in response to selective pressure. Moreover, the combination of natural evolutionary processes with chemically biased building blocks provides another strategy for the generation of biologically active peptides using microbial systems.

show abstract

mentioning

confidence: 99%

Evolution of cyclic peptide protease inhibitors

Young

Ahmad

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

122

127

View full text Add to dashboard Cite

show abstract

“…After 5 min, 30 ȝg/ml ampicillin was added to the cultures and growth was monitored at 37°C. ȕ Cyclic peptide or protein libraries are extremely useful as they can be exploited for genetic study or peptide inhibitor screening (Horswill and Benkovic, 2005). Studies have shown that cyclic proteins, with their N-and C-termini linked by a normal peptide bond, are easily generated using split inteins.…”

Section: Namementioning

confidence: 99%

A circularly permuted β-lactamase as a novel reporter for evaluation of protein cyclization efficiency

et al. 2008

View full text Add to dashboard Cite

Split inteins have been used as a versatile tool in protein engineering to mediate efficient in vivo and in vitro trans-splicing of a protein. The trans-splicing ability of split inteins was also applied to the in vivo cyclization of a protein. However, cyclization efficiency is dependent upon the type of split inteins employed and the conditions under which cyclization occur. In this study, a novel reporter system that easily measures the cyclization efficiency of split inteins was developed. For this purpose TEM-1 beta-lactamase was divided into two fragments (24-215 and 216-286 amino acids) and circularly permuted. The circularly permuted beta-lactamase expressed in Escherichia coli showed little beta-lactamase activity, most likely due to the structural modification of the protein. However, when the circularly permuted beta-lactamase was cyclized by the Synechocystis sp. PCC6803 DnaB split mini-intein, beta-lactamase activity both in vitro and in vivo was recovered. These results suggest that the novel reporter system can be exploited to develop new inteins with high efficiency of in vivo protein cyclization.

show abstract

“…The orthogonal aaRS/tRNA(CUA) pairs were expressed in Escherichia coli ( E. coli) in order to assign L- p -benzoylphenylalanine to the amber codon [46]. Additionally, the split intein catalyzed ligation of proteins and peptides (SICROPPS) method, which was developed by Benkovic's group [70, 71], was used to cyclize the backbone of a ribosomally synthesized peptide library containing L- p -benzoylphenylalanine. The activity-based in-cell selection of human immunodeficiency virus (HIV) protease inhibitors from the cyclic peptide library was performed by linking the protease inhibitory activity of a cyclic peptide to cell viability of the host E. coli .…”

Section: Selection Of Functional Nonstandard Peptides Generated Bymentioning

confidence: 99%

Genetically Encoded Libraries of Nonstandard Peptides

Kawakami

Murakami

2012

Journal of Nucleic Acids

View full text Add to dashboard Cite

The presence of a nonproteinogenic moiety in a nonstandard peptide often improves the biological properties of the peptide. Non-standard peptide libraries are therefore used to obtain valuable molecules for biological, therapeutic, and diagnostic applications. Highly diverse non-standard peptide libraries can be generated by chemically or enzymatically modifying standard peptide libraries synthesized by the ribosomal machinery, using posttranslational modifications. Alternatively, strategies for encoding non-proteinogenic amino acids into the genetic code have been developed for the direct ribosomal synthesis of non-standard peptide libraries. In the strategies for genetic code expansion, non-proteinogenic amino acids are assigned to the nonsense codons or 4-base codons in order to add these amino acids to the universal genetic code. In contrast, in the strategies for genetic code reprogramming, some proteinogenic amino acids are erased from the genetic code and non-proteinogenic amino acids are reassigned to the blank codons. Here, we discuss the generation of genetically encoded non-standard peptide libraries using these strategies and also review recent applications of these libraries to the selection of functional non-standard peptides.

show abstract

Cyclic Peptides, A Chemical Genetics Tool for Biologists

Cited by 44 publications

References 48 publications

Evolution of cyclic peptide protease inhibitors

Evolution of cyclic peptide protease inhibitors

A circularly permuted β-lactamase as a novel reporter for evaluation of protein cyclization efficiency

Genetically Encoded Libraries of Nonstandard Peptides

Contact Info

Product

Resources

About