title: The Acid/Base Profile of the Human Metabolome and Natural Products.
abstract: Human small molecule metabolites (the human metabolome) are a set of compounds that interact with at least one macromolecule in the biosphere. This study investigates the acid/base profile of the human metabolome, natural products and drugs, together with an analysis of their physicochemical properties. Ionisation constants (pKa values) are estimated for each compound and the identity of the ionisable functional groups in each set is determined. The acid/base and physicochemical property profile of the lipid component of the metabolome differed considerably to the other datasets. In contrast, the acid/base properties of non-lipid metabolites were found to be similar to both drugs and natural products. While the non-lipid metabolites have lower average ClogP values and more hydrogen bond donors than the other datasets, the distribution of physicochemical property values overlapped considerably with the drug dataset. Considering also that the non-lipid metabolites are of biochemical interest, their characteristics have great potential to influence the selection of screening compounds for drug discovery.
authors.affiliation: Medicinal Chemistry and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia tel: +61 3 99039537. David.Manallack@monash.edu.
authors.forename: David T
authors.initials: DT
authors.lastname: Manallack
authors.affiliation: Medicinal Chemistry and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia tel: +61 3 99039537.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Dennis
authors.affiliation: Medicinal Chemistry and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia tel: +61 3 99039537.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Kelly
authors.affiliation: Medicinal Chemistry and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia tel: +61 3 99039537.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Prankerd
authors.affiliation: Medicinal Chemistry and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia tel: +61 3 99039537.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Yuriev
authors.affiliation: Medicinal Chemistry and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia tel: +61 3 99039537.
authors.forename: David K
authors.initials: DK
authors.lastname: Chalmers
keywords: Acid; Acidity; Base; Basicity; Drug discovery; Human metabolome; Ionisation constant; Physicochemical properties; pKa