Open AccessAll-Purpose Containers? Lipid-Binding Protein – Drug Interactions
Author(s) -
Tiziana Beringhelli,
Elisabetta Gianazza,
Daniela Maggioni,
Sandra Scanu,
Chiara Parravicini,
Cristina Sensi,
Hugo L. Monaco,
Ivano Eberini
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0132096
Subject(s) - chemistry , binding site , docking (animal) , plasma protein binding , retinol binding protein , biochemistry , retinol , medicine , nursing , vitamin
The combined use of in vitro ( 19 F-NMR) and in silico (molecular docking) procedures demonstrates the affinity of a number of human calycins (lipid-binding proteins from ileum, liver, heart, adipose tissue and epidermis, and retinol-binding protein from intestine) for different drugs (mainly steroids and vastatins). Comparative evaluations on the complexes outline some of the features relevant for interaction (non-polar character of the drugs; amino acids and water molecules in the protein calyx most often involved in binding). Dissociation constants (K i ) for drugs typically lie in the same range as K i for natural ligands; in most instances (different proteins and docking conditions), vastatins are the strongest interactors, with atorvastatin ranking top in half of the cases. The affinity of some calycins for some of the vastatins is in the order of magnitude of the drug C max after systemic administration in humans. The possible biological implications of this feature are discussed in connection with drug delivery parameters (route of administration, binding to carrier proteins, distribution to, and accumulation in, human tissues).