title: Cell recognition enhanced enzyme hydrolysis of a model peptide-drug conjugate.
abstract: A model peptide-drug conjugate designed upon a beta-hairpin peptide with the alpha4beta1 integrin recognition sequence LDV appended to the N-terminus and a fluorescent model drug appended to the C-terminus. This model recognizes and binds to alpha4beta1 expressing cells and displays an enhanced rate of enzyme catalyzed hydrolytic model drug release in the presence of the cells compared to the rate in the absence of cells. The present work suggests that peptide-drug conjugate conformation change due to receptor binding may be a viable approach to targeted drug release.
authors.affiliation: Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, USA.
authors.forename: Phanidhara R
authors.initials: PR
authors.lastname: Kotamraj
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Bhaskara
authors.initials: B
authors.lastname: Jasti
authors.forename: Wade A
authors.initials: WA
authors.lastname: Russu
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003374:Coumarins / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D007202:Indicators and Reagents / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000378:metabolism; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*
chemical_list: C411664:7-amino-4-carbamoylmethylcoumarin; D003374:Coumarins; D004798:Enzymes; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D039041:Integrin alpha4beta1; D010455:Peptides