All-Purpose Containers? Lipid-Binding Protein – Drug Interactions

Abstract

The combined use of in vitro (19F-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 (Ki) for drugs typically lie in the same range as Ki 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 Cmax 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).

19F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis

“…In the literature, there are very few examples where the 19 F longitudinal relaxation rate has been used to assess the binding (e.g. Figueroa‐Villar and Tinoco and Beringhelli et al …”

Recent Advances on Small-Molecule Inhibitors of Lipocalin-like Proteins

“…FABP4, also called the adipose FABP (A-FABP) or aP2, is one of the most studied FABPs and several small-molecule FABP4 inhibitors have emerged. The binding affinity and specificity between FABP4 and natural ligands is mainly achieved by hydrogen bonding between the carboxylic end of fatty acids and Arg106 (via a water molecule), Arg126, and Tyr128. , Based on their chemical structures, FABP4 inhibitors can be classified into pyrazole, oxazole, imidazole, triazole, indole, benzimidazole, thiophene and thiazoles, pyrimidine, bicyclic pyridine and quinoxaline, urea and carbamoyl, sulfonamide, 2-aminobenzoic acid, and other compounds. , …”

“…The binding affinity and specificity between FABP4 and natural ligands is mainly achieved by hydrogen bonding between the carboxylic end of fatty acids and Arg106 (via a water molecule), Arg126, and Tyr128. 80,81 Based on their chemical structures, FABP4 inhibitors can be classified into pyrazole, oxazole, imidazole, triazole, indole, benzimidazole, thiophene and thiazoles, pyrimidine, bicyclic pyridine and quinoxaline, urea and carbamoyl, sulfonamide, 2-aminobenzoic acid, and other compounds. 82,83 BMS309403 (Figure 4, compound 35) is a well-known FABP4 inhibitor that belongs to the pyrazole group and has a K i of <2 nM.…”

Features and Possible Applications of Plant Lipid-Binding and Transfer Proteins

“…Lipid transfer proteins as well as human lipid-binding proteins calycins [ 119 ] are considered as possible drug delivery systems of unstable and water-insoluble drugs due to the following reasons. These proteins are characterized by high stability and bind a wide range of hydrophobic molecules, including drugs of various pharmacological groups.…”