Separation methods for estimating octanol–water partition coefficients

Poole, Salwa K.; Poole, Colin F.

doi:10.1016/j.jchromb.2003.08.032

Cited by 220 publications

(166 citation statements)

References 129 publications

(189 reference statements)

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“…Measurement of retention times is a rapid and convenient way to probe the surface properties of an analyte, and has recently been used to study the surface hydrophobicity of cyclic alanine-rich peptides [9]. In fact, retention time measurements converted to their respective capacity factors (and more specifically the logarithm of the capacity factors, log k') have been widely used as a method for estimating lipophilicity [32]. To begin exploring experimental markers, we first correlated the retention times of the peptides on reversed-phase high performance liquid chromatography (RP-HPLC) to their observed Caco-2 and PAMPA permeability, as shown in Figures 4A and 4B, respectively, as well as to their recovery from the permeability assays, as shown in Supplementary Figure 1.…”

Section: Resultsmentioning

confidence: 99%

Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability

Wang

Northfield

Swedberg

et al. 2015

European Journal of Medicinal Chemistry

108

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An increasing number of macrocyclic peptides that cross biological membranes are being reported, suggesting that it might be possible to develop peptides into orally bioavailable therapeutics; however, current understanding of what makes macrocyclic peptides cell permeable is still limited. Here, we synthesized 62 cyclic hexapeptides and characterized their permeability using in vitro assays commonly used to predict in vivo absorption rates, i.e. the Caco-2 and PAMPA assays. We correlated permeability with experimentally measured parameters of peptide conformation obtained using rapid methods based on chromatography and nuclear magnetic resonance spectroscopy. Based on these correlations, we propose a model describing the interplay between peptide permeability, lipophilicity and hydrogen bonding potential. Specifically, peptides with very high permeability have high lipophilicity and few solvent hydrogen bond interactions, whereas peptides with very low permeability have low lipophilicity or many solvent interactions. Our model is supported by molecular dynamics simulations of the cyclic peptides calculated in explicit solvent, providing a structural basis for the observed correlations. This prospective exploration into biomarkers of peptide permeability has the potential to unlock wider opportunities for development of peptides into drugs.3

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Section: Resultsmentioning

confidence: 99%

Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability

Wang

Northfield

Swedberg

et al. 2015

European Journal of Medicinal Chemistry

108

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“…The octanol/water distribution coefficients (logD) of allomaltol, thiomaltol, thioallomaltol were determined by the shake-flask method [20] phases, therefore is pH-dependent, while the pH-independent partition coefficient (P) is related to the neutral, non-ionized species which are transferred into the organic phase, thus P shows the equilibrium concentration ratio of the solute between the two phases [20,21].…”

Section: Determination Of the Distribution And Partition Coefficientsmentioning

confidence: 99%

Comparative solution equilibrium studies of anticancer gallium(III) complexes of 8-hydroxyquinoline and hydroxy(thio)pyrone ligands

Enyedy

Dömötör

Varga

et al. 2012

Journal of Inorganic Biochemistry

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“…P oct is a dimensionless figure usually expressed as a base 10 logarithm (Log P oct ) (7). Some authors sustain that an ideal Log P oct value is within 1 and 4 because in this range, the molecule has enough lipid affinity to cross membranes and enough water affinity to diffuse and dissolve in body fluids (6,(8)(9)(10). The value of Log P oct is only an estimate of the permeability since the said parameter does not consider absorption through transporters, which is an important absorption mechanism of drugs (3).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Membrane Permeability (PAMPA and Skin) of Benzimidazoles with Potential Cannabinoid Activity and their Relation with the Biopharmaceutics Classification System (BCS)

et al. 2011

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Abstract. The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P oct value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).

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Separation methods for estimating octanol–water partition coefficients

Cited by 220 publications

References 129 publications

Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability

Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability

Comparative solution equilibrium studies of anticancer gallium(III) complexes of 8-hydroxyquinoline and hydroxy(thio)pyrone ligands

Evaluation of the Membrane Permeability (PAMPA and Skin) of Benzimidazoles with Potential Cannabinoid Activity and their Relation with the Biopharmaceutics Classification System (BCS)

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