dc.contributor.author | Ng, Simon | |
dc.contributor.author | Lin, Edith | |
dc.contributor.author | Kitov, Pavel I. | |
dc.contributor.author | Tjhung, Katrina F. | |
dc.contributor.author | Gerlits, Oksana O. | |
dc.contributor.author | Deng, Lu | |
dc.contributor.author | Kasper, Brian | |
dc.contributor.author | Sood, Amika | |
dc.contributor.author | Paschal, Beth M. | |
dc.contributor.author | Zhang, Ping | |
dc.contributor.author | Ling, Chang-Chun | |
dc.contributor.author | Klassen, John S. | |
dc.contributor.author | Noren, Christopher J. | |
dc.contributor.author | Mahal, Lara K. | |
dc.contributor.author | Woods, Robert J. | |
dc.contributor.author | Coates, Leighton | |
dc.contributor.author | Derda, Ratmir | |
dc.date.accessioned | 2018-09-20T16:19:14Z | |
dc.date.available | 2018-09-20T16:19:14Z | |
dc.date.issued | 2015-04-29 | |
dc.identifier.citation | Ng, Simon; Lin, Edith; Kitov, Pavel I. Tjhung, Katrina F.; Gerlits, Oksana O.; Deng, Lu; Kasper, Brian; Sood, Amika; Paschal, Beth M.; Zhang, Ping; Ling, Chang-Chun; Klassen, John S.; Noren, Christopher J.; Mahal, Lara K.; Woods, Robert J.; Coates, Leighton; Derda, Ratmir (2015). Genetically encoded fragment-based discovery of glycopeptide ligands for carbohydrate-binding proteins. Journal of the American Chemical Society 137 (16), 5248-5251 | |
dc.identifier.issn | 0002-7863,1520-5126 | |
dc.identifier.uri | http://hdl.handle.net/10379/13115 | |
dc.description.abstract | 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 phagedisplayed 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 10(8) 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 alpha-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. | |
dc.publisher | American Chemical Society (ACS) | |
dc.relation.ispartof | Journal of the American Chemical Society | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | dc-sign | |
dc.subject | structural basis | |
dc.subject | concanavalin-a | |
dc.subject | library | |
dc.subject | phage | |
dc.subject | lectin | |
dc.subject | inhibitors | |
dc.subject | peptides | |
dc.subject | mimicry | |
dc.subject | glycobiology | |
dc.title | Genetically encoded fragment-based discovery of glycopeptide ligands for carbohydrate-binding proteins | |
dc.type | Article | |
dc.identifier.doi | 10.1021/ja511237n | |
dc.local.publishedsource | http://europepmc.org/articles/pmc5553193?pdf=render | |
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