{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:24:31Z","timestamp":1787055871619,"version":"build-2736575974"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p>There has been a growing focus on \u2018molecular chameleons\u2019 possessing structural flexibility; compounds that can dynamically adjust their conformations depending on the characteristics of the medium to either conceal or reveal polar parts in aqueous\/lipidic environments. Drug discovery has shifted in the past few decades toward more complex molecules, such as cyclic and macrocyclic peptides, as well as PROteolysis-TArgeting Chimeras (PROTACs). These large macromolecules are intended to balance cell permeability, aqueous solubility, and strong target binding capacity for effective pharmacokinetics; though they are more difficult to design than conventional small drug molecules. Molecular chameleons are useful for this task because of their capacity to adapt to various environments. The science underlying the structural flexibility of molecular chameleons, their growing significance, role in therapeutics and design strategies using contemporary tools are all covered in this review.<\/jats:p>","DOI":"10.3389\/fchem.2026.1886764","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:29:06Z","timestamp":1787052546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Flexible molecular chameleons: structural adaptability and therapeutic applications"],"prefix":"10.3389","volume":"14","author":[{"given":"Debosreeta","family":"Bose","sequence":"first","affiliation":[{"name":"Department of Basic Science and Humanities, Institute of Engineering and Management, University of Engineering and Management Kolkata, University Area","place":["Kolkata, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purvee","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"JNCT Professional University","place":["Bhopal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnishwar","family":"Girigoswami","sequence":"additional","affiliation":[{"name":"Medical Bionanotechnology, Faculty of Allied Health Sciences, Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE)","place":["Chennai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2121","DOI":"10.4155\/fmc.15.78","article-title":"Beyond cyclosporine A: conformation-Dependent passive membrane permeabilities of cyclic peptide natural products","volume":"7","author":"Ahlbach","year":"2015","journal-title":"Future Med. 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