A monosaccharide-modified peptide phage library for screening of ligands to carbohydrate-binding proteins

Arai, Keigo; Tsutsumi, Hiroshi; Mihara, Hisakazu

doi:10.1016/j.bmcl.2013.06.059

Cited by 35 publications

(46 citation statements)

References 38 publications

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“…115,116 In another approach, a P3 displayed library containing a free Cys was conjugated to mannose through the formation of a disulfide bond through the use of 2-(3-nitropyridyl disulfide ethyl)-mannopyranoside. 117 Such methods present an alternative form of synergistic binding mode obtained through the use of phage. Furthermore, synergistic binding based selections have also been performed with a phage-displayed Cys containing peptide library, conjugated to a pre-determined maleimide-functionalized ligand.…”

Section: Applications Of Modified Phagementioning

confidence: 99%

Chemically Modifying Viruses for Diverse Applications

Mohan

Weiss

2016

ACS Chem. Biol.

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Long fascinating to biologists, viruses offer nanometer-scale benchtops for building molecular-scale devices and materials. Viruses tolerate a wide-range of chemical modifications including reaction conditions, pH values, and temperatures. Recent examples of non-genetic manipulation of viral surfaces have extended viruses into applications ranging from biomedical imaging, drug delivery, tissue regeneration, and biosensors to materials for catalysis and energy generation. Chemical reactions on the phage surface include both covalent and non-covalent modifications, including some applied in conjunction with genetic modifications. Here, we survey viruses chemically augmented with capabilities limited only by imagination.

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Section: Applications Of Modified Phagementioning

confidence: 99%

Chemically Modifying Viruses for Diverse Applications

Mohan

Weiss

2016

ACS Chem. Biol.

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“…Here, we employ genetically encoded fragment-based discovery (GE-FBD) to identify peptide fragments (Figure 1) capable of forming a synergistic interaction together with a glycan moiety by taking advantage of the immense diversity of a genetically encoded peptide library. 14 …”

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confidence: 99%

“…14a Next, we employed deep-sequencing 15 and multiple panning controls to identify functional ligands, even after a single round of panning. In the proof-of-concept experiment with the model lectin, concanavalin A (ConA), we panned an α -mannopyranoside-oxime-terminated library (Man-X 7 , 1 ) against ConA and a control target (bovine serum albumin, BSA) (screens A and B , Figure 1B).…”

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confidence: 99%

Genetically Encoded Fragment-Based Discovery of Glycopeptide Ligands for Carbohydrate-Binding Proteins

Lin

Kitov

et al. 2015

J. Am. Chem. Soc.

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We describe an approach to accelerate the search for competitive inhibitors for carbohydrate-recognition domains (CRDs). Genetically encoded fragment-based discovery (GE-FBD) uses selection of phage-displayed glycopeptides to dock a glycan fragment at the CRD and guide selection of synergistic peptide motifs adjacent to the CRD. Starting from concanavalin A (ConA), a mannose (Man)-binding protein, as a bait, we narrowed a library of 108 glycopeptides to 86 leads that share a consensus motif, Man-WYD. Validation of synthetic leads yielded Man-WYDLF that exhibited 40–50-fold enhancement in affinity over methyl α-D-mannopyranoside (MeMan). Lectin array suggested specificity: Man-WYD derivative bound only to 3 out of 17 proteins—ConA, LcH, and PSA—that bind to Man. An X-ray structure of ConA:Man-WYD proved that the trimannoside core and Man-WYD exhibit identical CRD docking, but their extra-CRD binding modes are significantly different. Still, they have comparable affinity and selectivity for various Man-binding proteins. The intriguing observation provides new insight into functional mimicry of carbohydrates by peptide ligands. GE-FBD may provide an alternative to rapidly search for competitive inhibitors for lectins.

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“…glycopeptides with high affinity for carbohydrate-binding proteins [17,18]. Mihara and Tsutsumi et al created glycopeptide ligands of a mannose-binding protein by conjugating mannose functionalized with pyridyldithiol to a cysteine residue within a randomized peptide by a disulfide exchange reaction (Figure 2c) [17].…”

Section: Current Opinion In Chemical Biologymentioning

confidence: 98%