ArticleScientific reports2018
Compositional Bias in Naïve and Chemically-modified Phage-Displayed Libraries uncovered by Paired-end Deep Sequencing.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 41 citations in OpenAlex.
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- Depth of Sequencing Plays a Determining Role in the Characterization of Phage Display Peptide Libraries by NGS.International journal of molecular sciences · 2023Article
- Pattern enrichment analysis for phage selection of stapled peptide ligands.Chemical science · 2022Article
- PDL1Binder: Identifying programmed cell death ligand 1 binding peptides by incorporating next-generation phage display data and different peptide descriptors.Frontiers in microbiology · 2022Article
- Learning the structure-activity relationship (SAR) of the Wittig reaction from genetically-encoded substrates.Chemical science · 2021Article
- Expanding the Chemical Diversity of Genetically Encoded Libraries.ACS combinatorial science · 2020Article
- InteractomeSeq: a web server for the identification and profiling of domains and epitopes from phage display and next generation sequencing data.Nucleic acids research · 2020Article
- Exploring the Post-translational Enzymology of PaaA by mRNA Display.Journal of the American Chemical Society · 2020Article
- An amber obligate active site-directed ligand evolution technique for phage display.Nature communications · 2020Article
- Evolving a Peptide: Library Platforms and Diversification Strategies.International journal of molecular sciences · 2019Review
- SAROTUP: a suite of tools for finding potential target-unrelated peptides from phage display data.International journal of biological sciences · 2019Article
- Peptide design by optimization on a data-parameterized protein interaction landscape.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Inhibitors of protein-protein interactions (PPIs): an analysis of scaffold choices and buried surface area.Current opinion in chemical biology · 2018Review
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the composition of a genetically-encoded (GE) library is instrumental to the success of ligand discovery. In this manuscript, we investigate the bias in GE-libraries of linear, macrocyclic and chemically post-translationally modified (cPTM) tetrapeptides displayed on the M13KE platform, which are produced via trinucleotide cassette synthesis (19 codons) and NNK-randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector {L} (extension and ligation of synthetic DNA into the vector), naïve libraries {N} (transformation of the ligated vector into the bacteria followed by expression of the library for 4.5 hours to yield a "naïve" library), and libraries chemically modified by aldehyde ligation and cysteine macrocyclization {M} characterized by paired-end deep sequencing, detected a significant drop in diversity in {L} → {N}, but only a minor compositional difference in {S} → {L} and {N} → {M}. Libraries expressed at the N-terminus of phage protein pIII censored positively charged amino acids Arg and Lys; libraries expressed between pIII domains N1 and N2 overcame Arg/Lys-censorship but introduced new bias towards Gly and Ser. Interrogation of biases arising from cPTM by aldehyde ligation and cysteine macrocyclization unveiled censorship of sequences with Ser/Phe. Analogous analysis can be used to explore library diversity in new display platforms and optimize cPTM of these libraries.
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