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Cited by 172

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Accurate de novo design of membrane-traversing macrocycles

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Bhardwaj, Gaurav, O’Connor, Jacob, Rettie, Stephen, Huang, Yen-Hua, Ramelot, Theresa A., Mulligan, Vikram Khipple, Alpkilic, Gizem Gokce, Palmer, Jonathan, Bera, Asim K., Bick, Matthew J., Di Piazza, Maddalena, Li, Xinting, Hosseinzadeh, Parisa, Craven, Timothy W., Tejero, Roberto, Lauko, Anna, Choi, Ryan, Glynn, Calina, Dong, Linlin, Griffin, Robert, van Voorhis, Wesley C., Rodriguez, Jose, Stewart, Lance, Montelione, Gaetano T., Craik, David, Baker, David·2022·Cell
DOI 10.1016/j.cell.2022.07.019
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Abstract

cm/s. Designs with exposed NH groups can be made membrane permeable through the design of an alternative isoenergetic fully hydrogen-bonded state favored in the lipid membrane. The ability to robustly design membrane-permeable and orally bioavailable peptides with high structural accuracy should contribute to the next generation of designed macrocycle therapeutics.

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Research works printed but not linked: 45

  1. Adolf-Bryfogle, J., Labonte, J.W., Kraft, J.C., Shapovalov, M., Raemisch, S., Lütteke, T., DiMaio, F., Bahl, C.D., Pallesen, J., King, N.P., et al. (2021). Growing Glycans in Rosetta: Accurate de novo glycan modeling, density fitting, and rational sequon design. · DOI
  2. Baxter, 1997, Temperature dependence of 1H chemical shifts in proteins, J. Biomol. NMR, 9, 359, 10.1023/A:1018334207887 · DOI · Paper page
  3. Bhardwaj, 2016, Accurate de novo design of hyperstable constrained peptides, Nature, 538, 329, 10.1038/nature19791 · DOI · Paper page
  4. Bockus, 2015, Probing the physicochemical boundaries of cell permeability and oral bioavailability in lipophilic macrocycles inspired by natural products, J. Med. Chem., 58, 4581, 10.1021/acs.jmedchem.5b00128 · DOI
  5. Cierpicki, 2001, Amide proton temperature coefficients as hydrogen bond indicators in proteins, J. Biomol. NMR, 21, 249, 10.1023/A:1012911329730 · DOI · Paper page
  6. Coutsias, 2004, A kinematic view of loop closure, J. Comput. Chem., 25, 510, 10.1002/jcc.10416 · DOI · Paper page
  7. Delaglio, 1995, NMRPipe: a multidimensional spectral processing system based on UNIX pipes, J. Biomol. NMR, 6, 277, 10.1007/BF00197809 · DOI · Paper page
  8. Di, 2003, High throughput artificial membrane permeability assay for blood-brain barrier, Eur. J. Med. Chem., 38, 223, 10.1016/S0223-5234(03)00012-6 · DOI · Paper page
  9. Emsley, 2004, Coot: model-building tools for molecular graphics, Acta Crystallogr. D Biol. Crystallogr., 60, 2126, 10.1107/S0907444904019158 · DOI · Paper page
  10. Fleishman, 2011, RosettaScripts: a scripting language interface to the Rosetta macromolecular modeling suite, PLoS One, 6, 10.1371/journal.pone.0020161 · DOI · Paper page
  11. Fouché, 2016, Design and development of a cyclic decapeptide scaffold with suitable properties for bioavailability and oral exposure, ChemMedChem, 11, 1048, 10.1002/cmdc.201600082 · DOI
  12. Ganguly, 2012, Direct evidence for CH···π interaction mediated stabilization of Pro-cisPro bond in peptides with Pro-Pro-aromatic motifs, J. Am. Chem. Soc., 134, 4661, 10.1021/ja209334v · DOI
  13. Grathwohl, 1981, NMR studies of the rates of proline cis–trans isomerization in oligopeptides, Biopolymers, 20, 2623, 10.1002/bip.1981.360201209 · DOI · Paper page
  14. Güntert, 1997, Torsion angle dynamics for NMR structure calculation with the new program DYANA, J. Mol. Biol., 273, 283, 10.1006/jmbi.1997.1284 · DOI · Paper page
  15. Herrmann, 2002, Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA, J. Mol. Biol., 319, 209, 10.1016/S0022-2836(02)00241-3 · DOI · Paper page
  16. Hewitt, 2015, Cell-permeable cyclic peptides from synthetic libraries inspired by natural products, J. Am. Chem. Soc., 137, 715, 10.1021/ja508766b · DOI · Paper page
  17. Hill, 2014, Cyclic penta- and Hexaleucine peptides without N-methylation are orally absorbed, ACS Med. Chem. Lett., 5, 1148, 10.1021/ml5002823 · DOI
  18. Hosseinzadeh, 2017, Comprehensive computational design of ordered peptide macrocycles, Science, 358, 1461, 10.1126/science.aap7577 · DOI · Paper page
  19. Hosseinzadeh, 2021, Anchor extension: a structure-guided approach to design cyclic peptides targeting enzyme active sites, Nat. Commun., 12, 3384, 10.1038/s41467-021-23609-8 · DOI · Paper page
  20. Hübschle, 2011, ShelXle: a Qt graphical user interface for SHELXL, J. Appl. Crystallogr., 44, 1281, 10.1107/S0021889811043202 · DOI · Paper page
  21. Hunter, 2007, Matplotlib: A 2D Graphics, Environment, 9, 90
  22. Lee, 2015, NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy, Bioinformatics, 31, 1325, 10.1093/bioinformatics/btu830 · DOI · Paper page
  23. Mandell, 2009, Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling, Nat. Methods, 6, 551, 10.1038/nmeth0809-551 · DOI · Paper page
  24. Marelli, 2015, cis-Peptide Bonds: A Key for intestinal Permeability of Peptides?, Chemistry, 21, 15148, 10.1002/chem.201501600 · DOI
  25. McKinney, W. (2010). Data structures for statistical computing in python. In Proceedings of the 9th Python in Science Conference, (Austin, TX), pp. 51–56. · DOI · Paper page
  26. Mulligan, 2020, The emerging role of computational design in peptide macrocycle drug discovery. Expert Opin, Drug Discov, 15, 833
  27. Mulligan, 2021, Computationally designed peptide macrocycle inhibitors of New Delhi metallo-β-lactamase 1, Proc. Natl. Acad. Sci. USA, 118, 10.1073/pnas.2012800118 · DOI
  28. Muttenthaler, 2021, Trends in peptide drug discovery, Nat. Rev. Drug Discov, 20, 309, 10.1038/s41573-020-00135-8 · DOI · Paper page
  29. Nielsen, 2017, Orally absorbed cyclic peptides, Chem. Rev., 117, 8094, 10.1021/acs.chemrev.6b00838 · DOI · Paper page
  30. Ovadia, 2011, The effect of multiple N-methylation on intestinal permeability of cyclic hexapeptides, Mol. Pharm., 8, 479, 10.1021/mp1003306 · DOI
  31. Park, H., Bradley, P., Greisen, P., Jr, Liu, Y., Mulligan, V.K., Kim, D.E., Baker, D., and DiMaio, F. (2016). Simultaneous Optimization of Biomolecular Energy Functions on Features from Small Molecules and Macromolecules. J. Chem. Theory Comput. 12, 6201–6212. · DOI · Paper page
  32. Peraro, 2018, Getting. In emerging methods and design principles for cell-penetrant peptides, Angew. Chem., 130, 12042, 10.1002/ange.201801361 · DOI
  33. Pye, 2017, Nonclassical size dependence of permeation defines bounds for passive adsorption of large drug molecules, J. Med. Chem., 60, 1665, 10.1021/acs.jmedchem.6b01483 · DOI
  34. Rand, 2012, Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance, Medchemcomm, 3, 1282, 10.1039/C2MD20203D · DOI
  35. Renfrew, 2012, Incorporation of noncanonical amino acids into Rosetta and use in computational protein-peptide interface design, PLoS One, 7, 10.1371/journal.pone.0032637 · DOI
  36. Rezai, 2006, Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides, J. Am. Chem. Soc., 128, 14073, 10.1021/ja063076p · DOI · Paper page
  37. Sevin, 2013, Accelerated Caco-2 cell permeability model for drug discovery, J. Pharmacol. Toxicol. Methods, 68, 334, 10.1016/j.vascn.2013.07.004 · DOI
  38. Tejero, 2013, PDBStat: a universal restraint converter and restraint analysis software package for protein NMR, J. Biomol. NMR, 56, 337, 10.1007/s10858-013-9753-7 · DOI
  39. Vögeli, 2007, Limits on variations in protein backbone dynamics from precise measurements of scalar couplings, J. Am. Chem. Soc., 129, 9377, 10.1021/ja070324o · DOI
  40. Wang, 2014, Rational design and synthesis of an orally bioavailable peptide guided by NMR amide temperature coefficients, Proc. Natl. Acad. Sci. USA, 111, 17504, 10.1073/pnas.1417611111 · DOI · Paper page
  41. Wang, 2015, Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability, Eur. J. Med. Chem., 97, 202, 10.1016/j.ejmech.2015.04.049 · DOI
  42. Wang, 2018, Conformational flexibility is a determinant of permeability for cyclosporin, J. Phys. Chem. B, 122, 2261, 10.1021/acs.jpcb.7b12419 · DOI
  43. White, 2011, On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds, Nat. Chem. Biol., 7, 810, 10.1038/nchembio.664 · DOI · Paper page
  44. Winn, M.D., Refinemen, M.-L.S., Pannu, N.J., Murshudov, G.N., and Others (2001). CCP4 v6. 3.0 Program References. Acta Crystallogr. 57, 122–133. · DOI · Paper page
  45. Yilmaz, 2015, NMR structure calculation for all small molecule ligands and non-standard residues from the PDB Chemical Component Dictionary, J. Biomol. NMR, 63, 21, 10.1007/s10858-015-9959-y · DOI

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Metadata

Authors
Bhardwaj, G., O’Connor, J., Rettie, S., Huang, Y.-H., Ramelot, T. A., Mulligan, V. K., Alpkilic, G. G., Palmer, J., Bera, A. K., Bick, M. J., Di Piazza, M., Li, X., Hosseinzadeh, P., Craven, T. W., Tejero, R., Lauko, A., Choi, R., Glynn, C., Dong, L., Griffin, R., van Voorhis, W. C., Rodriguez, J., Stewart, L., Montelione, G. T., Craik, D., & Baker, D.
Venue
Cell
Publisher
Elsevier BV
Published
2022-09
Volume
185
Issue
19
Pages
3520-3532.e26
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2022.07.019
OpenAlex
W4293461777
Cited by
172
References
6
FWCI
9.60
Type
journal article
Language
en
Open access
hybrid
Licence
Funders
  • U.S. Department of Defense
  • Howard Hughes Medical Institute
  • Defense Threat Reduction Agency (HDTRA1-19-1-0003)
  • National Institute of General Medical Sciences (P30 GM124165)
  • National Institutes of Health (R35-GM141818, R01GM120574, R01AG063845, F32GM120791-02)
  • Simons Foundation
  • U.S. Department of Energy
  • Argonne National Laboratory
  • University of Washington
  • Ted Conferences LLC
  • Office of Science (DE-AC02-06CH11357)
  • Bill and Melinda Gates Foundation (INV-010680)
  • Washington Research Foundation

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CoChat. (2026). Citation check: Accurate de novo design of membrane-traversing macrocycles. https://app.cochat.ai/papers/10.1016/j.cell.2022.07.019
The paper
Bhardwaj, G., O’Connor, J., Rettie, S., Huang, Y.-H., Ramelot, T. A., Mulligan, V. K., Alpkilic, G. G., Palmer, J., Bera, A. K., Bick, M. J., Di Piazza, M., Li, X., Hosseinzadeh, P., Craven, T. W., Tejero, R., Lauko, A., Choi, R., Glynn, C., Dong, L., . . . Baker, D. (2022). Accurate de novo design of membrane-traversing macrocycles. Cell. https://doi.org/10.1016/j.cell.2022.07.019

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