pH-dependency of basic ligand binding to α1-acid glycoprotein (orosomucoid)

Urien, Saı̈k; Brée, F.; Testa, Bernard; Tillement, J P

doi:10.1042/bj2800277

Cited by 39 publications

(22 citation statements)

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“…A third explanation lies in the potentially different binding modalities of LAs and those drug classes examined by Kaliszan et al (1995), principally antihistamines and class II antiarrythmics. The model of Kaliszan et al (1995) is also inconsistent with a report on the binding of unfractionated AGP to six amphipathic amines: two antihypertensives, two antidepressants, an antipsychotic, and a coronary vasodilator (Urien et al, 1991). The neutral forms of these drugs bound to AGP more tightly than did their protonated counterparts by factors of 5 to 20.…”

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confidence: 52%

Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α₁-Acid Glycoprotein

Taheri

Cogswell²,

Gent³

et al. 2003

J Pharmacol Exp Ther

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Understanding the interaction of local anesthetics (LAs) with plasma proteins is essential to understanding their systemic pharmacology and toxicology. The molecular determinants of LA binding to the major variant (F1*S) of human ␣ 1 -acid glycoprotein (AGP) were therefore investigated spectrofluorometrically using whole AGP and a novel, F1*S variant-selective probe previously developed in our laboratory. Equilibriumcompetitive displacement of this probe by LAs, observed by the recovery of AGP's fluorescence as the quenching probe was displaced from its high-affinity site, was characterized by inhibitory dissociation constants for the various LAs. The importance of electrostatic factors was assessed by examining the pH dependent binding of an ionizable LA, lidocaine, using the quaternary lidocaine derivative triethylammonium chloride] to control for pH dependent ionization of AGP. Uncharged lidocaine bound with at least 8 times the affinity of protonated lidocaine (K D ϭ 4.0 Ϯ 0.6 M and Ͼ32 M, respectively). This result is inconsistent with the current model of the AGP-binding site, which depicts a buried pocket having a negatively charged region that interacts with the amino termini of basic drugs. Consistent with the model, however, two sets of structurally homologous LAs (mepivacaine, ropivacaine, bupivacaine, and lidocaine, RAD-240, RAD-241, RAD-242, L-30, W-6603) demonstrated a strong positive correlation between hydrophobicity (measured as the octanol:buffer partition coefficient of the neutral species) and their free energies of dissociation. Given that the tertiary structure of AGP has proven refractory to resolution, these structure-activity studies should contribute to understanding the nature of the binding site on this important protein.Understanding the interaction of local anesthetics with plasma proteins is essential to predicting their systemic pharmacology and toxicology. Many basic drugs, including local anesthetics (LAs) and class I antiarrythmics, are bound in blood principally or in part by AGP (Routledge, 1986;Stanski and Watkins, 1986;Wood, 1986;Kremer et al., 1988). The binding of a drug to a plasma protein reduces its free fraction in serum, thus reducing its availability for active uptake or diffusion into surrounding tissue and significantly influencing its pharmacokinetics, toxicity, etc. (Wood, 1986).For example, the local anesthetic bupivacaine binds tightly to AGP (with K D ϭ 1 M) (Essassi et al., 1989), and this binding may mitigate the systemic toxicity of bupivacaine (Wulf et al., 1991;Mazoit et al., 1996).Indeed, altered pharmacokinetics have been observed following the binding of AGP to the LAs lidocaine and cocaine, and the same holds true with other clinically relevant amphipathic amines: amitriptyline, chlorpromazine, nicardipine, and verapamil (Benet and Hoener, 2002). For example, AGP concentration has been shown to correlate inversely with the free fraction of the LA ropivacaine 60 min after epidural injection (Porter et al., 2001). Also, one of the AGP variants...

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confidence: 52%

Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α₁-Acid Glycoprotein

Taheri

Cogswell²,

Gent³

et al. 2003

J Pharmacol Exp Ther

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“…Both proteins have only three His residues with a protein length of 201 amino acids. Also, 40% of these proteins contain carbohy- drates [26] which might mask the His groups, and that could explain why these proteins were not retained on the IMAC columns but were retained by the RP column. The protein apolipoprotein A-II does not have any His group on its surface to have retention on the IDA-metal columns.…”

Section: Highlights Of the Retention Of Some Typical Proteins On The mentioning

confidence: 97%

Reduction of protein concentration range difference followed by multicolumn fractionation prior to 2‐DE and LC‐MS/MS profiling of serum proteins

Selvaraju

Rassi

2011

Electrophoresis

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This article is concerned with the reduction of protein concentration range differences by the peptide beads library technology (ProteoMiner™ or "equalizer" technology), which in principle allows the enrichment of proteins to the same concentration level (i.e. protein equalizer) regardless of the original protein abundance in a given biological fluid such as human serum, which is the subject of our investigation. After the equalization step, the captured proteins from human serum were fractionated on a series of tandem monolithic columns with surface-bound iminodiacetic acid ligands to which three different metal ions, namely, Zn²+, Ni²+ and Cu²+ were immobilized to yield the so-called immobilized metal affinity chromatography columns. These three monolithic columns were connected to a reversed-phase column packed with polystyrene divinyl benzene beads. Aliquots taken from the four collected fractions from the four tandem columns were subsequently fractionated by 2-DE. Also, aliquots from the four collected fractions were tryptically digested and analyzed by LC-MS/MS. The strategy of subsequent fractionation on the four tandem columns after equalization allowed the identification of more proteins than simply using the equalization by ProteoMiner™ . The equalizer technology was compared to the immuno-subtraction approach. While the ProteoMiner™ technology is superior in terms of the overall number of captured proteins, it only complements the immuno-subtraction approach since the latter can capture the proteins that were not captured by the former.

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“…16,19,26 A study of the pH dependency of several basic drugs to AGP found that the drugs in the neutral form have a markedly higher affinity for AGP than the protonated forms, which suggests that hydrophobic interactions dominate high-affinity binding to AGP. 27 Recently, a thermodynamic study found that the entropic drive to AGP binding increases with decreasing global polarity of drugs, whereas the enthalpic drive increases with increasing polarity. 28 Here, we may expect that the protein domain is responsible for stereoselectivity.…”

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confidence: 99%

Effect of sialic acid residues of human ?1-acid glycoprotein on stereoselectivity in basic drug-protein binding

et al. 1997

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pH-dependency of basic ligand binding to α1-acid glycoprotein (orosomucoid)

Cited by 39 publications

References 9 publications

Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α₁-Acid Glycoprotein

Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α₁-Acid Glycoprotein

Reduction of protein concentration range difference followed by multicolumn fractionation prior to 2‐DE and LC‐MS/MS profiling of serum proteins

Effect of sialic acid residues of human ?1-acid glycoprotein on stereoselectivity in basic drug-protein binding

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pH-dependency of basic ligand binding to α1-acid glycoprotein (orosomucoid)

Cited by 39 publications

References 9 publications

Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α1-Acid Glycoprotein

Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α1-Acid Glycoprotein

Reduction of protein concentration range difference followed by multicolumn fractionation prior to 2‐DE and LC‐MS/MS profiling of serum proteins

Effect of sialic acid residues of human ?1-acid glycoprotein on stereoselectivity in basic drug-protein binding

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Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α₁-Acid Glycoprotein

Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α₁-Acid Glycoprotein