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Cell\u2010penetrating peptides (CPPs) are short oligomeric peptides capable of translocating across the cell membrane while simultaneously employing multiple mechanisms of entry. Most CPPs exist as disordered structures in solution and may adopt a helical conformation on interaction with cell membrane, vital to their penetrative capability. Herein, we report a series of cationic helical amphipathic peptides (CHAPs), which are topologically constrained to be helical. The peptides were tested against cervical and breast cancer cells for their cell penetration and drug delivery potential. The cellular uptake of CHAP peptides is independent of temperature and energy availability. The activity of the peptides is biocompatible in bovine serum. CHAPs delivered functional methotrexate (MTX) inside the cell as CHAP\u2010MTX conjugates. CHAP\u2010MTX conjugates were more toxic to cancer cells than MTX alone. However, the CHAP\u2010MTX conjugates were less toxic to HEK\u2010293 cells compared with the cancer cells suggesting higher affinity towards cancer cells.<\/jats:p>","DOI":"10.1002\/psc.3244","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T07:32:38Z","timestamp":1583307158000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Conformationally constrained peptides for drug delivery"],"prefix":"10.1002","volume":"26","author":[{"given":"Gaurav","family":"Jerath","sequence":"first","affiliation":[{"name":"Molecular Informatics and Design Laboratory, Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati  Guwahati India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruchika","family":"Goyal","sequence":"additional","affiliation":[{"name":"Molecular Informatics and Design Laboratory, Department of Biosciences and Bioengineering Indian 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