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Rapid microwave-assisted CNBr cleavage of bead-bound peptides

Lee, Su Seong and Lim, Jaehong and Cha, Junhoe and Tan, Sylvia and Heath, James R. (2008) Rapid microwave-assisted CNBr cleavage of bead-bound peptides. Journal of Combinatorial Chemistry, 10 (6). pp. 807-809. ISSN 1520-4766. PMCID PMC2720530. https://resolver.caltech.edu/CaltechAUTHORS:LEEjcc08

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Abstract

Large libraries of peptides, cyclic peptides, and other molecules are standard tools for the discovery of drugs, molecular probes, and affinity reagents. In particular, one-bead-one-compound (OBOC) libraries,(1) prepared by the split-and-mix method,(2) provide access to a broad chemical space with a minimum of reagents. Once such a library has been screened against the target of interest, the chemical identity of the library elements on the hit beads is identified. For peptide libraries and their variants, mass spectrometry (MS) based peptide sequencing provides the most rapid method for such analysis. OBOC libraries are constructed in a number of ways to facilitate MS analysis,(3-5) but one common feature is that the peptide must be cleaved from the bead prior to being introduced into the mass spectrometer. While a number of chemical(6) and photochemical(7) cleavage strategies have been developed, the most common strategy is to incorporate a CNBr-cleavable methionine-linker group at the C-terminus of the peptide.(8) CNBr cleavage has also been widely used in proteomics to cleave proteins.(9) With such chemistry, up to 100 beads from an OBOC peptide library can be sequenced in a 24 h period.(10) A large fraction of that time, however, is devoted to the CNBr cleavage step. Standard literature protocols describe CNBr cleavage as requiring between 12 and 24 h, using 20−30 μL of 0.25 M CNBr in 70% aqueous formic acid at room temperature.(11) Although the CNBr cleavage time may be reduced to 2−4 h at elevated temperatures (47 °C), significant side-products may be generated.(12) All reports that we have found that describe CNBr cleavage chemistry from single beads have used the same conditions as for proteomics, although the two chemical processes are not necessarily equivalent.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/cc800113dDOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720530PubMed CentralArticle
ORCID:
AuthorORCID
Heath, James R.0000-0001-5356-4385
Additional Information:© 2008 American Chemical Society. Received July 4, 2008. Publication Date (Web): September 24, 2008. We acknowledge Heather Agnew and Rosemary Rohde for the assistance provided with obtaining Edman degradation peptide sequencing results. This work was supported by the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore), with additional support (J.R.H.) from the National Cancer Institute Grant No. 5U54 CA119347 (J.R.H., P.I.) and a subcontract from the Mitre Corporation.
Funders:
Funding AgencyGrant Number
Agency for Science, Technology and Research (A*STAR)UNSPECIFIED
NIH5U54 CA119347
Mitre CorporationUNSPECIFIED
National Cancer InstituteUNSPECIFIED
Subject Keywords:organic-synthesis; combinatorial libraries; cyanogens-bromide; ladder-synthesis; chemistry; spectrometry; irradiation; efficiency; catalysis; proteins
Issue or Number:6
PubMed Central ID:PMC2720530
Record Number:CaltechAUTHORS:LEEjcc08
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:LEEjcc08
Official Citation:Rapid Microwave-Assisted CNBr Cleavage of Bead-Bound Peptides. Su Seong Lee, Jaehong Lim, Junhoe Cha, Sylvia Tan, and James R. Heath. Journal of Combinatorial Chemistry 2008 10 (6), 807-809. DOI: 10.1021/cc800113d
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13818
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:02 Apr 2009 22:26
Last Modified:23 Dec 2019 17:00

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