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Titolo:
Structural requirements for the biosynthesis of backbone cyclic peptide libraries
Autore:
Scott, CP; Abel-Santos, E; Jones, AD; Benkovic, SJ;
Indirizzi:
Penn State Univ, Dept Chem, University Pk, PA 16802 USA Penn State Univ University Pk PA USA 16802 m, University Pk, PA 16802 USA Penn State Univ, Davey Lab 152, Penn State Intercollegiate Mass Spectrometry, University Pk, PA 16802 USA Penn State Univ University Pk PA USA 16802y, University Pk, PA 16802 USA
Titolo Testata:
CHEMISTRY & BIOLOGY
fascicolo: 8, volume: 8, anno: 2001,
pagine: 801 - 815
SICI:
1074-5521(200108)8:8<801:SRFTBO>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENETIC SELECTION; COMBINATORIAL LIBRARIES; SPLIT INTEIN; DNAE GENE; INHIBITORS; PROTEINS; CHEMISTRY; PCC6803; FORMAT; SCREEN;
Keywords:
combinatorial chemistry; cyclic peptide; intein; SICLOPPS; small molecule;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Benkovic, SJ Penn State Univ, Dept Chem, 414 Wartik Lab, University Pk, PA16802 USA Penn State Univ 414 Wartik Lab University Pk PA USA 16802 USA
Citazione:
C.P. Scott et al., "Structural requirements for the biosynthesis of backbone cyclic peptide libraries", CHEM BIOL, 8(8), 2001, pp. 801-815

Abstract

Background: Combinatorial methods for the production of molecular libraries are an important source of ligand diversity for chemical biology. Synthetic methods focus on the production of small molecules that must traverse the cell membrane to elicit a response. Genetic methods enable intracellular ligand production, but products must typically be large molecules in order to withstand cellular catabolism. Here we describe an intein-based approachto biosynthesis of backbone cyclic peptide libraries that combines the strengths of synthetic and genetic methods. Results: Through site-directed mutagenesis we show that the DnaE intein from Synechoeystis sp. PCC6803 is very promiscuous with respect to peptide substrate composition, and can generate cyclic products ranging from four to nine amino acids. Libraries with five variable amino acids and either one or four fixed residues bwere prepared, yielding between 10(7) and 10(8) transformants. The majority of randomly selected clones from each library gave cyclic products. Conclusions: We have developed a versatile method for producing intracellular libraries of small, stable cyclic peptides. Genetic encoding enables facile manipulation of vast numbers of compounds, while low molecular weight ensures ready pharmacophore identification. The demonstrated flexibility ofthe method towards both peptide length and composition makes it a valuableaddition to existing methods for generating ligand diversity. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/08/20 alle ore 19:49:57