Synthesis and Screening of One-Bead-One-Compound Cyclic Peptide Libraries

Qian, Ziqing; Upadhyaya, Punit; Pei, Dehua

doi:10.1007/978-1-4939-2020-4_3

Cited by 40 publications

(28 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With an extended surface area for binding, they are highly suited to inhibit protein–protein interactions. The discovery of cyclic peptides through combinatorial approaches is typically carried out by methods to screen large libraries of either chemically synthesized or genetically encoded peptides, such as one‐bead‐one‐compound screening, or display techniques, such as phage and yeast surface display . More recent approaches also exploit the potential of semisynthetic libraries to increase the accessible chemical space.…”

Section: Figurementioning

confidence: 99%

Bacterial Cell‐Surface Display of Semisynthetic Cyclic Peptides

et al. 2018

View full text Add to dashboard Cite

Semisynthetic cyclic peptides containing both non-proteinogenic building blocks, as the synthetic part, and a genetically encoded sequence amenable to DNA-based randomization hold great potential to expand the chemical space in the quest for novel bioactive peptides. Key to an efficient selection of novel binders to biomacromolecules is a robust method to link their genotype and phenotype. A novel bacterial cell surface display technology has been developed to present cyclic peptides composed of synthetic and genetically encoded fragments in their backbones. The fragments were combined by protein trans-splicing and intramolecular oxime ligation. To this end, a split intein half and an unnatural amino acid were displayed with the genetically encoded part on the surface of Escherichia coli. Addition of the synthetic fragment equipped with the split intein partner and an aminooxy moiety, as well as the application of a pH-shift protocol, resulted in the onsurface formation of the semisynthetic cyclic peptide. This approach will serve for the generation of cyclic peptide libraries suitable for selection by fluorescence-activated cell sorting, and more generally enables chemical modification of proteins on the bacterial surface.

show abstract

Section: Figurementioning

confidence: 99%

Bacterial Cell‐Surface Display of Semisynthetic Cyclic Peptides

et al. 2018

View full text Add to dashboard Cite

show abstract

“…One key feature of such libraries is their enormous theoretical chemical diversity by including various non-natural amino acids in the synthesis. However, due to synthetic and analytical constraints, the size of such libraries is limited to about 10 7 [28].…”

Section: Peptide Discovery Platformmentioning

confidence: 99%

Encoded Library Technologies as Integrated Lead Finding Platforms for Drug Discovery

et al. 2019

View full text Add to dashboard Cite

The scope of targets investigated in pharmaceutical research is continuously moving into uncharted territory. Consequently, finding suitable chemical matter with current compound collections is proving increasingly difficult. Encoded library technologies enable the rapid exploration of large chemical space for the identification of ligands for such targets. These binders facilitate drug discovery projects both as tools for target validation, structural elucidation and assay development as well as starting points for medicinal chemistry. Novartis internalized two complementing encoded library platforms to accelerate the initiation of its drug discovery programs. For the identification of low-molecular weight ligands, we apply DNA-encoded libraries. In addition, encoded peptide libraries are employed to identify cyclic peptides. This review discusses how we apply these two platforms in our research and why we consider it beneficial to run both pipelines in-house.

show abstract

“…Fluorescent activated cell sorting (FACS) or magnetic bead sorting are now used for positive bead isolation followed by sequence analysis by partial Edman degradation and mass spectrometry (PED-MS) or MS alone. [6,7] Enhancing diversity through molecular biology…”

Section: Combinatorial Chemistry-based Screeningmentioning

confidence: 99%

Exploring sequence space: harnessing chemical and biological diversity towards new peptide leads

Obexer

Walport

Suga

2017

Current Opinion in Chemical Biology

View full text Add to dashboard Cite

From their early roots in natural products, peptides now represent an expanding class of novel drugs. Their modular structures make them ideal candidates for pooled library screening approaches. Key technologies for library generation and screening, such as SICLOPPS, phage display and mRNA display, give unparalleled access to tight binding peptides. Through combination with genetic code reprogramming and chemical modifications, access to more natural product-like libraries, spanning non-canonical peptide space, is readily achievable. Recent advances in these fields enable introduction of diverse non-standard motifs, such as cyclisation and backbone methylations. Peptide discovery platforms now allow robust access to potent, highly functionalised peptides against virtually any protein of interest, with typical binding constants in the nanomolar range. Application of these optimised platforms in a drug discovery setting has the potential to significantly accelerate identification of new leads.

show abstract

Synthesis and Screening of One-Bead-One-Compound Cyclic Peptide Libraries

Cited by 40 publications

References 28 publications

Bacterial Cell‐Surface Display of Semisynthetic Cyclic Peptides

Bacterial Cell‐Surface Display of Semisynthetic Cyclic Peptides

Encoded Library Technologies as Integrated Lead Finding Platforms for Drug Discovery

Exploring sequence space: harnessing chemical and biological diversity towards new peptide leads

Contact Info

Product

Resources

About