dc.contributor.author | Liu, Fa | |
dc.contributor.author | Park, Jung-Eun | |
dc.contributor.author | Qian, Wen-Jian | |
dc.contributor.author | Scharow, Andrej | |
dc.contributor.author | Berg, Thorsten | |
dc.contributor.author | Lee, Kyung S. | |
dc.contributor.author | Lim, Daniel Cham-Chin | |
dc.contributor.author | Yaffe, Michael B | |
dc.contributor.author | Burke, Terrence R. | |
dc.date.accessioned | 2014-02-28T17:45:56Z | |
dc.date.available | 2014-02-28T17:45:56Z | |
dc.date.issued | 2012-01 | |
dc.date.submitted | 2011-11 | |
dc.identifier.issn | 1554-8929 | |
dc.identifier.issn | 1554-8937 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/85193 | |
dc.description.abstract | In an effort to develop improved binding antagonists of the polo-like kinase 1 (Plk1) polo-box domain (PBD), we optimized interactions of the known high affinity 5-mer peptide PLHSpT using oxime-based post solid-phase peptide diversification of the N-terminal Pro residue. This allowed us to achieve up to two orders of magnitude potency enhancement. An X-ray crystal structure of the highest affinity analogue in complex with Plk1 PBD revealed new binding interactions in a hydrophobic channel that had been occluded in X-ray structures of the unliganded protein. This study represents an important example where amino acid modification by post solid-phase oxime ligation can facilitate the development of protein–protein interaction inhibitors by identifying new binding pockets that would not otherwise be accessible to coded amino acid residues. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant R01 GM60594) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant ES015339) | en_US |
dc.language.iso | en_US | |
dc.publisher | American Chemical Society (ACS) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1021/cb200469a | en_US |
dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
dc.source | PMC | en_US |
dc.title | Identification of High Affinity Polo-like Kinase 1 (Plk1) Polo-box Domain Binding Peptides Using Oxime-Based Diversification | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Liu, Fa, Jung-Eun Park, Wen-Jian Qian, Dan Lim, Andrej Scharow, Thorsten Berg, Michael B. Yaffe, Kyung S. Lee, and Terrence R. Burke. “Identification of High Affinity Polo-Like Kinase 1 (Plk1) Polo-Box Domain Binding Peptides Using Oxime-Based Diversification.” ACS Chemical Biology 7, no. 5 (May 18, 2012): 805–810. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Lim, Daniel Cham-Chin | en_US |
dc.contributor.mitauthor | Yaffe, Michael B. | en_US |
dc.relation.journal | ACS Chemical Biology | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Liu, Fa; Park, Jung-Eun; Qian, Wen-Jian; Lim, Dan; Scharow, Andrej; Berg, Thorsten; Yaffe, Michael B.; Lee, Kyung S.; Burke, Terrence R. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-9547-3251 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |