{"entity": "researcher", "timestamp": "2026-08-22T07:49:29.459Z", "family": "Matsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0002-9094-2581", "affiliations": ["Department of Pharmacy, Uppsala University, 752 37 Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/57286366d8624b689b3809ede3cab002.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/57286366d8624b689b3809ede3cab002"}}, "publications": [{"entity": "publication", "iuid": "1ad2bf41881a4e2daa1429d43a224b07", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1ad2bf41881a4e2daa1429d43a224b07.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1ad2bf41881a4e2daa1429d43a224b07"}}, "title": "Structural dynamics of therapeutic nucleic acids with phosphorothioate backbone modifications.", "authors": [{"family": "Carlesso", "given": "Antonio", "initials": "A"}, {"family": "H\u00f6rberg", "given": "Johanna", "initials": "J"}, {"family": "Deganutti", "given": "Giuseppe", "initials": "G"}, {"family": "Reymer", "given": "Anna", "initials": "A", "orcid": "0000-0001-8458-7918", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4b0749399be94ff5ad459ae8a57b1da4.json"}}, {"family": "Matsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0002-9094-2581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57286366d8624b689b3809ede3cab002.json"}}], "type": "journal article", "published": "2024-06-00", "journal": {"title": "NAR Genomics and Bioinformatics", "issn": "2631-9268", "volume": "6", "issue": "2", "pages": "lqae058", "issn-l": null}, "abstract": "Antisense oligonucleotides (ASOs) offer ground-breaking possibilities for selective pharmacological intervention for any gene product-related disease. Therapeutic ASOs contain extensive chemical modifications that improve stability to enzymatic cleavage and modulate binding affinity relative to natural RNA/DNA. Molecular dynamics (MD) simulation can provide valuable insights into how such modifications affect ASO conformational sampling and target binding. However, force field parameters for chemically modified nucleic acids (NAs) are still underdeveloped. To bridge this gap, we developed parameters to allow simulations of ASOs with the widely applied phosphorothioate (PS) backbone modification, and validated these in extensive all-atom MD simulations of relevant PS-modified NA systems representing B-DNA, RNA, and DNA/RNA hybrid duplex structures. Compared to the corresponding natural NAs, single PS substitutions had marginal effects on the ordered DNA/RNA duplex, whereas substantial effects of phosphorothioation were observed in single-stranded RNA and B-DNA, corroborated by the experimentally derived structure data. We find that PS-modified NAs shift between high and low twist states, which could affect target recognition and protein interactions for phosphorothioated oligonucleotides. Furthermore, conformational sampling was markedly altered in the PS-modified ssRNA system compared to that of the natural oligonucleotide, indicating sequence-dependent effects on conformational preference that may in turn influence duplex formation.", "doi": "10.1093/nargab/lqae058", "pmid": "38800826", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11127634"}, {"db": "pii", "key": "lqae058"}], "notes": [], "created": "2026-08-20T09:42:56.763Z", "modified": "2026-08-20T09:42:56.863Z"}, {"entity": "publication", "iuid": "74cc2b53a1ee42b69b44f8ac027993a9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/74cc2b53a1ee42b69b44f8ac027993a9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/74cc2b53a1ee42b69b44f8ac027993a9"}}, "title": "Challenges in Permeability Assessment for Oral Drug Product Development.", "authors": [{"family": "Koziolek", "given": "Mirko", "initials": "M", "orcid": "0000-0002-1385-182X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f67968c2ce34387887a6fad5394fd70.json"}}, {"family": "Augustijns", "given": "Patrick", "initials": "P", "orcid": "0000-0003-2595-388X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/621417a631354dd98830bba151305a61.json"}}, {"family": "Berger", "given": "Constantin", "initials": "C"}, {"family": "Cristofoletti", "given": "Rodrigo", "initials": "R"}, {"family": "Dahlgren", "given": "David", "initials": "D", "orcid": "0000-0002-5586-2906", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/33cf48a71e1049d0bda062492e6d6db9.json"}}, {"family": "Keemink", "given": "Janneke", "initials": "J", "orcid": "0009-0006-7359-5350", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/580dcee0c1cf41e79441f656ab64636e.json"}}, {"family": "Matsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0002-9094-2581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57286366d8624b689b3809ede3cab002.json"}}, {"family": "McCartney", "given": "Fiona", "initials": "F", "orcid": "0000-0002-5834-7950", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/90f3915c3a3440e3924bc5e4a400a3f8.json"}}, {"family": "Metzger", "given": "Marco", "initials": "M"}, {"family": "Mezler", "given": "Mario", "initials": "M", "orcid": "0000-0002-7253-0962", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e35234fa8fa9454a94ccbe838545b705.json"}}, {"family": "Niessen", "given": "Janis", "initials": "J"}, {"family": "Polli", "given": "James E", "initials": "JE", "orcid": "0000-0002-5274-4314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f80c7a2779f94dc2a5da6681d19ed343.json"}}, {"family": "Vertzoni", "given": "Maria", "initials": "M", "orcid": "0000-0003-4463-2459", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c861eb88fd8c4deaac1d6c26c597660d.json"}}, {"family": "Weitschies", "given": "Werner", "initials": "W", "orcid": "0000-0003-3492-7747", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/415c40d6737a48439048d89d9df0ea48.json"}}, {"family": "Dressman", "given": "Jennifer", "initials": "J"}], "type": "journal article", "published": "2023-09-28", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "15", "issue": "10", "issn-l": null}, "abstract": "Drug permeation across the intestinal epithelium is a prerequisite for successful oral drug delivery. The increased interest in oral administration of peptides, as well as poorly soluble and poorly permeable compounds such as drugs for targeted protein degradation, have made permeability a key parameter in oral drug product development. This review describes the various in vitro, in silico and in vivo methodologies that are applied to determine drug permeability in the human gastrointestinal tract and identifies how they are applied in the different stages of drug development. The various methods used to predict, estimate or measure permeability values, ranging from in silico and in vitro methods all the way to studies in animals and humans, are discussed with regard to their advantages, limitations and applications. A special focus is put on novel techniques such as computational approaches, gut-on-chip models and human tissue-based models, where significant progress has been made in the last few years. In addition, the impact of permeability estimations on PK predictions in PBPK modeling, the degree to which excipients can affect drug permeability in clinical studies and the requirements for colonic drug absorption are addressed.", "doi": "10.3390/pharmaceutics15102397", "pmid": "37896157", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10609725"}, {"db": "pii", "key": "pharmaceutics15102397"}], "notes": [], "created": "2026-08-20T13:43:06.743Z", "modified": "2026-08-20T13:43:07.186Z"}, {"entity": "publication", "iuid": "77e1d906fe0d4fc4a4519f8d9f6a303b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/77e1d906fe0d4fc4a4519f8d9f6a303b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/77e1d906fe0d4fc4a4519f8d9f6a303b"}}, "title": "Influence of Proteome Profiles and Intracellular Drug Exposure on Differences in CYP Activity in Donor-Matched Human Liver Microsomes and Hepatocytes.", "authors": [{"family": "Wegler", "given": "Christine", "initials": "C", "orcid": "0000-0002-2810-7518", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fcb45d19c52847f19bd5c0aa296afe10.json"}}, {"family": "Matsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0002-9094-2581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57286366d8624b689b3809ede3cab002.json"}}, {"family": "Krogstad", "given": "Veronica", "initials": "V"}, {"family": "Urdzik", "given": "Jozef", "initials": "J"}, {"family": "Christensen", "given": "Hege", "initials": "H"}, {"family": "Andersson", "given": "Tommy B", "initials": "TB"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9908209a413a4088b6bf44a924d27319.json"}}], "type": "journal article", "published": "2021-04-05", "journal": {"title": "Mol. Pharm.", "issn": "1543-8392", "volume": "18", "issue": "4", "pages": "1792-1805", "issn-l": "1543-8384"}, "abstract": "Human liver microsomes (HLM) and human hepatocytes (HH) are important in vitro systems for studies of intrinsic drug clearance (CLint) in the liver. However, the CLint values are often in disagreement for these two systems. Here, we investigated these differences in a side-by-side comparison of drug metabolism in HLM and HH prepared from 15 matched donors. Protein expression and intracellular unbound drug concentration (Kpuu) effects on the CLint were investigated for five prototypical probe substrates (bupropion-CYP2B6, diclofenac-CYP2C9, omeprazole-CYP2C19, bufuralol-CYP2D6, and midazolam-CYP3A4). The samples were donor-matched to compensate for inter-individual variability but still showed systematic differences in CLint. Global proteomics analysis outlined differences in HLM from HH and homogenates of human liver (HL), indicating variable enrichment of ER-localized cytochrome P450 (CYP) enzymes in the HLM preparation. This suggests that the HLM may not equally and accurately capture metabolic capacity for all CYPs. Scaling CLint with CYP amounts and Kpuu could only partly explain the discordance in absolute values of CLint for the five substrates. Nevertheless, scaling with CYP amounts improved the agreement in rank order for the majority of the substrates. Other factors, such as contribution of additional enzymes and variability in the proportions of active and inactive CYP enzymes in HLM and HH, may have to be considered to avoid the use of empirical scaling factors for prediction of drug metabolism.", "doi": "10.1021/acs.molpharmaceut.1c00053", "pmid": "33739838", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8041379"}], "notes": [], "created": "2026-08-20T08:12:29.330Z", "modified": "2026-08-20T08:12:29.465Z"}, {"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"}]}