{"entity": "researcher", "timestamp": "2026-08-22T08:30:47.926Z", "family": "Over", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0002-9185-5420", "affiliations": ["Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D Gothenburg, M\u00f6lndal, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/89c861c6ffe04434a2e43a28b0cf45a1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/89c861c6ffe04434a2e43a28b0cf45a1"}}, "publications": [{"entity": "publication", "iuid": "6d7b380da35f43aaad92b1e9df5b27a9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6d7b380da35f43aaad92b1e9df5b27a9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6d7b380da35f43aaad92b1e9df5b27a9"}}, "title": "Structural and conformational determinants of macrocycle cell permeability.", "authors": [{"family": "Over", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0002-9185-5420", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/89c861c6ffe04434a2e43a28b0cf45a1.json"}}, {"family": "Matsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0002-9094-2581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57286366d8624b689b3809ede3cab002.json"}}, {"family": "Tyrchan", "given": "Christian", "initials": "C"}, {"family": "Artursson", "given": "Per", "initials": "P"}, {"family": "Doak", "given": "Bradley C", "initials": "BC"}, {"family": "Foley", "given": "Michael A", "initials": "MA"}, {"family": "Hilgendorf", "given": "Constanze", "initials": "C"}, {"family": "Johnston", "given": "Stephen E", "initials": "SE"}, {"family": "Lee", "given": "Maurice D", "initials": "MD"}, {"family": "Lewis", "given": "Richard J", "initials": "RJ"}, {"family": "McCarren", "given": "Patrick", "initials": "P"}, {"family": "Muncipinto", "given": "Giovanni", "initials": "G"}, {"family": "Norinder", "given": "Ulf", "initials": "U"}, {"family": "Perry", "given": "Matthew W D", "initials": "MW"}, {"family": "Duvall", "given": "Jeremy R", "initials": "JR"}, {"family": "Kihlberg", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2016-12-00", "journal": {"title": "Nat. Chem. Biol.", "issn": "1552-4469", "volume": "12", "issue": "12", "pages": "1065-1074", "issn-l": "1552-4450"}, "abstract": "Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 non-peptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure-permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.", "doi": "10.1038/nchembio.2203", "pmid": "27748751", "labels": [], "xrefs": [{"db": "pii", "key": "nchembio.2203"}, {"db": "PubChem-Substance", "key": "318122242"}, {"db": "PubChem-Substance", "key": "318122253"}, {"db": "PubChem-Substance", "key": "318122264"}, {"db": "PubChem-Substance", "key": "318122269"}, {"db": "PubChem-Substance", "key": "318122270"}, {"db": "PubChem-Substance", "key": "318122271"}, {"db": "PubChem-Substance", "key": "318122272"}, {"db": "PubChem-Substance", "key": "318122273"}, {"db": "PubChem-Substance", "key": "318122274"}, {"db": "PubChem-Substance", "key": "318122243"}, {"db": "PubChem-Substance", "key": "318122244"}, {"db": "PubChem-Substance", "key": "318122245"}, {"db": "PubChem-Substance", "key": "318122246"}, {"db": "PubChem-Substance", "key": "318122247"}, {"db": "PubChem-Substance", "key": "318122248"}, {"db": "PubChem-Substance", "key": "318122249"}, {"db": "PubChem-Substance", "key": "318122250"}, {"db": "PubChem-Substance", "key": "318122251"}, {"db": "PubChem-Substance", "key": "318122252"}, {"db": "PubChem-Substance", "key": "318122254"}, {"db": "PubChem-Substance", "key": "318122255"}, {"db": "PubChem-Substance", "key": "318122256"}, {"db": "PubChem-Substance", "key": "318122257"}, {"db": "PubChem-Substance", "key": "318122258"}, {"db": "PubChem-Substance", "key": "318122259"}, {"db": "PubChem-Substance", "key": "318122260"}, {"db": "PubChem-Substance", "key": "318122261"}, {"db": "PubChem-Substance", "key": "318122262"}, {"db": "PubChem-Substance", "key": "318122263"}, {"db": "PubChem-Substance", "key": "318122265"}, {"db": "PubChem-Substance", "key": "318122266"}, {"db": "PubChem-Substance", "key": "318122267"}, {"db": "PubChem-Substance", "key": "318122268"}], "notes": [], "created": "2018-12-05T09:25:45.404Z", "modified": "2026-08-21T11:40:08.032Z"}]}