Nuclear Magnetic Relaxation Study of Intermolecular Complexes. The Mechanism of Penicillin Binding to Serum Albumin<sup>1a</sup>

Fischer, James J.; Jardetzky, Oleg

doi:10.1021/ja01092a040

Cited by 162 publications

(60 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…'H NMR spectra of plasma will be of routine The binspin-echo methods which, in effect, act as 'mobiliding of small molecules to proteins, for example, ty filters', allowing only peaks from protons with can lead to severe broadening of resonances long TZ values to appear in the spectrum [l-5]. [12,13]. There have already been suggestions that 'H NMR spectra of plasma will be of diagnostic clinical value.…”

Section: Introductionmentioning

confidence: 99%

NMR‐invisible lactate in blood plasma

et al. 1988

View full text Add to dashboard Cite

Resonances for lactate are broadened in 500 MHz 1H NMR spectra of human blood plasma and only about one‐third is visible in Hahn spin‐echo spectra. Similar effects are observed for some other carboxylate anions. Lactate added to the high‐M r fraction of plasma can give rise to peaks which are too broad to observe in either single‐pulse or spin‐echo spectra. Addition of agents such as NH4Cl of SDS dramatically increases the intensities of lactate peaks. Some glycoproteins appear to broaden lactate resonances.

show abstract

Section: Introductionmentioning

confidence: 99%

NMR‐invisible lactate in blood plasma

et al. 1988

View full text Add to dashboard Cite

show abstract

“…8 In this work, however, rapid exchange between both states was observed, since a single peak was observed and this peak was a weighted average of both states. In slow-exchange systems, Tz-measurement by CPMG method is difficult because of the modulation effect of repeated P pulse^.…”

Section: Spin-spin Relaxation Rate Of Npmentioning

confidence: 70%

Interaction between drugs and water‐soluble polymers: VIII. Binding position of naproxen to bovine serum albumin

1995

View full text Add to dashboard Cite

SYNOPSISThe interaction between naproxen (NP) and bovine serum albumin (BSA) was investigated by equilibrium dialysis. Since the binding constant of NP to BSA was independent of ionic strength and decreased with increase of alkyl chain length of fatty acid added, the interaction between NP and BSA was considered to be due to hydrophobic mechanism. Chemical shifts in 'H-NMR spectra of NP were independent of the concentration of NP and addition of BSA. Spin-lattice relaxation time (TI) and spin-spin relaxation time ( T z ) of respective protons of NP were independent of the concentration, but depended on the concentration of BSA added. The binding position of N P to BSA was considered to involve the hydrophobic aromatic moiety of NP from the ratio of spin-spin relaxation rates I NTRO DUCT1 0 NIn the series of studies concerning interaction between drugs and water-soluble polymers,'-7 equilibrium dialysis was the conventional method to study the binding constant (k), the number (n) of binding sites, and the nature of binding (hydrophobic or hydrophilic). On the other hand, NMR especially the ratio of the spin-spin relaxation rate (l/Tz) of the free drug to that of the bound drug was the most useful parameter to determine the binding position of the drug with bovine serum albumin (BSA)2-5. In the early study: the Tz value was estimated from peak width at half height, which contained an error from inhomogeneity of magnetic field. In order to avoid this error, Hahng devised the spin-echo method. Furthermore, the Carr-Purcell-MeiboomGill (CPMG) method'" was developed in order to overcome the effect of molecular diffusion and phase distortion which occurred in the spin-echo method. However, there are two controversial ~~ * To whom all correspondence should be addressed. points in CPMG method. One is the deformation of phase by J-modulation, and the other is the modulation induced by repeated application of the A pulse. In our experiments, the A pulses were applied at time intervals short enough to prevent the modulation. Unfortunately, a high concentration ( 5 mmol/L) of the drug was required because of low sensitivity of NMR. While the concentration (= 0.1 mmol/L) of BSA should be lower than that of the drug because broad peaks in NMR spectrum were observed under high concentration comparable to the drug. It was known that BSA had a globular molecular structure folding hydrophobic aromatic parts inward," and that hydrophobic binding of the drug with BSA decreased by chemical modification of tryptophan and tyrosine on molecular surface of BSA.12 In the presence of BSA, each peak on the NMR spectrum was not shown by superposition of narrow peak for free state and broad peak for bound state; instead it was single peak as weighted average of both states, so that rapid exchange between both states was considered. Therefore, the binding position of the drug to BSA could be determined even if the ratio of the concentration of the drug to that of protein was large (E 50). In

show abstract

“…NMR has also been used to monitor compound binding to albumin, with the earliest report being from Oleg Jardetzky's lab in the study of penicillin binding to albumin. [34] However, most of these methods can neither identify the binding site on HSA involved in the interaction, nor distinguish between high affinity binding to a single site and low af- Figure 2. The 3D structure of human serum albumin [80] with known binding sites indicated.…”

Section: Measuring Compound Affinity For Human Serum Albuminmentioning

confidence: 99%

NMR in Pharmacokinetic and Pharmacodynamic Profiling

2005

View full text Add to dashboard Cite

Nuclear Magnetic Relaxation Study of Intermolecular Complexes. The Mechanism of Penicillin Binding to Serum Albumin^1a

Cited by 162 publications

References 3 publications

NMR‐invisible lactate in blood plasma

NMR‐invisible lactate in blood plasma

Interaction between drugs and water‐soluble polymers: VIII. Binding position of naproxen to bovine serum albumin

NMR in Pharmacokinetic and Pharmacodynamic Profiling

Contact Info

Product

Resources

About

Nuclear Magnetic Relaxation Study of Intermolecular Complexes. The Mechanism of Penicillin Binding to Serum Albumin1a

Cited by 162 publications

References 3 publications

NMR‐invisible lactate in blood plasma

NMR‐invisible lactate in blood plasma

Interaction between drugs and water‐soluble polymers: VIII. Binding position of naproxen to bovine serum albumin

NMR in Pharmacokinetic and Pharmacodynamic Profiling

Contact Info

Product

Resources

About

Nuclear Magnetic Relaxation Study of Intermolecular Complexes. The Mechanism of Penicillin Binding to Serum Albumin^1a