The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Stitched α-Helical Peptides via Bis Ring-Closing Metathesis
Abstract
Conformationally stabilized α-helical peptides are capable of inhibiting disease-relevant intracellular or extracellular protein-protein interactions in vivo. We have previously reported that the employment of ring-closing metathesis to introduce a single all-hydrocarbon staple along one face of an α-helical peptide greatly increases α-helical content, binding affinity to a target protein, cell penetration through active transport, and resistance to proteolytic degradation. In an effort to improve upon this technology for stabilizing a peptide in a bioactive α-helical conformation, we report the discovery of an efficient and selective bis ring-closing metathesis reaction leading to peptides bearing multiple contiguous staples connected by a central spiro ring junction. Circular dichroism spectroscopy, NMR, and computational analyses have been used to investigate the conformation of these "stitched" peptides, which are shown to exhibit remarkable thermal stabilities. Likewise, trypsin proteolysis assays confirm the achievement of a structural rigidity unmatched by peptides bearing a single staple. Furthermore, fluorescence-activated cell sorting (FACS) and confocal microscopy assays demonstrate that stitched peptides display superior cell penetrating ability compared to their stapled counterparts, suggesting that this technology may be useful not only in the context of enhancing the drug-like properties of α-helical peptides but also in producing potent agents for the intracellular delivery of proteins and oligonucleotides.
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Cites
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Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., & Korsmeyer, S. J. (2004) · Science · doi:10.1126/science.1099191 · Cited by 1,349
Self-citationSchafmeister, C. E., Po, J., & Verdine, G. L. (2000) · Journal of the American Chemical Society · doi:10.1021/ja000563a · Cited by 1,037
Self-citationDirect inhibition of the NOTCH transcription factor complex
Moellering, R. E., Cornejo, M., Davis, T. N., Bianco, C. D., Aster, J. C., Blacklow, S. C., Kung, A. L., Gilliland, D. G., Verdine, G. L., & Bradner, J. E. (2009) · Nature · doi:10.1038/nature08543 · Cited by 752
Self-citationGeneral approach to the synthesis of short .alpha.-helical peptides
Jackson, D. Y., King, D. S., Chmielewski, J., Singh, S., & Schultz, P. G. (1991) · Journal of the American Chemical Society · doi:10.1021/ja00024a067 · Cited by 313
A Highly Stable Short α-Helix Constrained by a Main-Chain Hydrogen-Bond Surrogate
Chapman, R. N., Dimartino, G., & Arora, P. S. (2004) · Journal of the American Chemical Society · doi:10.1021/ja0466659 · Cited by 228
Leduc, A.-M., Trent, J. O., Wittliff, J. L., Bramlett, K. S., Briggs, S. L., Chirgadze, N. Y., Wang, Y., Burris, T. P., & Spatola, A. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1934759100 · Cited by 222
Systematic Analysis of Helical Protein Interfaces Reveals Targets for Synthetic Inhibitors
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Rational Design of Proteolytically Stable, Cell-Permeable Peptide-Based Selective Mcl-1 Inhibitors
Muppidi, A., Doi, K., Edwardraja, S., Drake, E. J., Gulick, A. M., Wang, H.-G., & Lin, Q. (2012) · Journal of the American Chemical Society · doi:10.1021/ja306864v · Cited by 156
Cited by
Pelay‐Gimeno, M., Glas, A., Koch, O., & Grossmann, T. N. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201412070 · Cited by 717
New Modalities for Challenging Targets in Drug Discovery
Valeur, E., Guéret, S. M., Adihou, H., Gopalakrishnan, R., Lemurell, M., Waldmann, H., Grossmann, T. N., & Plowright, A. T. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201611914 · Cited by 382
Hydrocarbon Stapled Peptides as Modulators of Biological Function
Cromm, P. M., Spiegel, J., & Grossmann, T. N. (2015) · ACS Chemical Biology · doi:10.1021/cb501020r · Cited by 290
Arylation Chemistry for Bioconjugation
Zhang, C., Vinogradova, E. V., Spokoyny, A. M., Buchwald, S. L., & Pentelute, B. L. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201806009 · Cited by 265
A “cross-stitched” peptide with improved helicity and proteolytic stability
Speltz, T. E., Mayne, C. G., Fanning, S. W., Siddiqui, Z., Tajkhorshid, E., Greene, G. L., & Moore, T. W. (2018) · Organic & Biomolecular Chemistry · doi:10.1039/c8ob00790j · Cited by 39
Metadata
- Authors
- Hilinski, G. J., Kim, Y.-W., Hong, J., Kutchukian, P. S., Crenshaw, C. M., Berkovitch, S. S., Chang, A., Ham, S., & Verdine, G. L.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-08-21
- Volume
- 136
- Issue
- 35
- Pages
- 12314-12322
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2312496963
- Cited by
- 164
- References
- 9
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Open access
- closed
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- Hilinski, G. J., Kim, Y.-W., Hong, J., Kutchukian, P. S., Crenshaw, C. M., Berkovitch, S. S., Chang, A., Ham, S., & Verdine, G. L. (2014). Stitched α-Helical Peptides via Bis Ring-Closing Metathesis. Journal of the American Chemical Society. https://doi.org/10.1021/ja505141j
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