Synthesis of Spin-Labelled Procaine and its Derivatives

Hideg, Kálmán; Lex, L.; Hankovszky, H. O.; Tigyi, J

doi:10.1080/00397917908064194

Cited by 9 publications

(3 citation statements)

References 7 publications

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“…Unlabeled benzocaine, procaine, and tetracaine were from Sigma (St. Louis, MO). Spin-labeled local anesthetic analogues I-IV (see Chart I) were synthesized as described in Hideg et al (1979). The other spin-label derivatives, V-X (see Chart I), were synthesized by analogous methods, and their detailed characterization will be reported elsewhere.…”

Section: Methodsmentioning

confidence: 99%

“…Here we have examined the interaction of local anesthetics in AChR-rich membrane vesicles from Torpedo marmorata, making use of the designed series of spin-labeled local anesthetic analogues shown in Chart I (Hideg et al, 1979). The effects of partitioning between the aqueous and membrane phases and motional restriction at the intramembranous surface of the integral protein in the AChR-rich membranes have been separated, and it is shown that a certain population of the local anesthetics are in contact with the AChR in a manner similar to that of fatty acids and phospholipids.…”

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confidence: 99%

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Association of spin-labeled local anesthetics at the hydrophobic surface of the acetylcholine receptor in native membranes from Torpedo marmorata

Horváth¹,

Arias²,

Hankovszky³

et al. 1990

Biochemistry

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The interactions between a series of spin-labeled local anesthetic analogues and the nicotinic acetylcholine receptor (AChR) have been investigated by means of electron spin resonance (ESR) and fluorescence spectroscopy. The paramagnetic local anesthetic analogues quenched the intrinsic tryptophan fluorescence of AChR-rich membranes in an agonist-dependent manner, demonstrating a direct interaction with the AChR. The quenching efficiency was greater for the benzocaine than for the thioprocaine analogue. The protein was found to restrict directly the molecular motion of the spin-labeled analogues, as seen by the appearance of a highly anisotropic component in the ESR spectrum. The relative affinity of the population of local anesthetic probes which interacts directly with the integral protein of the AChR-rich membranes was calculated on the basis of relative association constants, Kr, determined by ESR. By comparison with the relative association constant for spin-labeled phospholipid, Kro, it was possible to differentiate between local anesthetic analogues interacting with high (Kr/Kro greater than 2), intermediate (Kr/Kro = 1.6-1.9), and low (Kr/Kro less than or equal to 1.3) specificity and to calculate the fraction of protein-associated probe in each case. Differences were observed in the presence of agonist (0.1 mM carbamylcholine) with some, but not all, of the spin-labeled derivatives. The role of the protonatable diethylammonium group in the specificity of the interaction of the procaine and thioprocaine analogues was investigated. Only in the uncharged form, or in the charged form at high ionic strength, was there a preferential association of these two local anesthetic analogues.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Association of spin-labeled local anesthetics at the hydrophobic surface of the acetylcholine receptor in native membranes from Torpedo marmorata

Horváth¹,

Arias²,

Hankovszky³

et al. 1990

Biochemistry

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“…Spin-labelled local anaesthetics (analogues of benzocaine, procaine, tetracaine, procainamide and procaine thioester; [47]) are synthesised as described in [48]. These hydrophobic anaesthetics localise to the lipid-protein interface in membranes enriched with the nicotinic acetylcholine receptor [49].…”

Section: Synthesis Of Spin-labelled Fatty Acids Phospholipids and Glmentioning

confidence: 99%

Electron spin resonance in membrane research: Protein–lipid interactions

Marsh

2008

Methods

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Different electron spin resonance (ESR) methods are described that allow determination of the stoichiometry and selectivity of interaction of spin-labelled lipids with integral transmembrane peptides or proteins, and also with peripheral surface-binding membrane proteins or peptides. In addition, ESR methods for determining the exchange rates of spin-labelled lipids at the protein-lipid interface are described, as well as methods to detect penetration of surface-binding peptides into the hydrophobic membrane core. Instrumental requirements are considered, and also sample handling, spin-labelling techniques and the synthesis of spin-labelled lipids.

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