Protolytic properties of polyamine wasp toxin analogues studied by 13C NMR spectroscopy
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Protolytic properties of polyamine wasp toxin analogues studied by 13C NMR spectroscopy. / Strømgaard, Kristian; Piazzi, Lorna; Olsen, Christian A; Franzyk, Henrik; Jaroszewski, Jerzy W.
In: Magnetic Resonance in Chemistry, Vol. 44, No. 11, 2006, p. 1013-22.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Protolytic properties of polyamine wasp toxin analogues studied by 13C NMR spectroscopy
AU - Strømgaard, Kristian
AU - Piazzi, Lorna
AU - Olsen, Christian A
AU - Franzyk, Henrik
AU - Jaroszewski, Jerzy W
N1 - Copyright 2006 John Wiley & Sons, Ltd.
PY - 2006
Y1 - 2006
N2 - Acid-base properties of the natural polyamine wasp toxin PhTX-433 (1) and seven synthetic analogues [PhTX-343 (2), PhTX-334 (3), PhTX-443 (4), PhTX-434 (5), PhTX-344 (6), PhTX-444 (7), and PhTX-333 (8)], each having four protolytic sites, were characterized by 13C NMR spectroscopy. Nonlinear, multiparameter, simultaneous fit of all chemical shift data obtained from the NMR titration curves yielded macroscopic pKa values as well as intrinsic chemical shift data of all differently protonated macrospecies. Analyses of the chemical shift data demonstrated strong interactions between all four sites and provided information about complex relationships between chemical shift values and protonation state. Deprotonation of fully protonated forms starts at the central amino group of the polyamine moiety, and the extent of this trend depends on the distance to the flanking, protonated amino groups. The pKa1 values of 1-8 are in the range 8.2-9.4. Hence, some of the toxins are incompletely protonated at the pH and ionic strength conditions used for assessment of their interactions with ionotropic glutamate and nicotinic acetylcholine receptors, and the degree of protonation is expected to have pharmacological importance in the ion-channel binding event.
AB - Acid-base properties of the natural polyamine wasp toxin PhTX-433 (1) and seven synthetic analogues [PhTX-343 (2), PhTX-334 (3), PhTX-443 (4), PhTX-434 (5), PhTX-344 (6), PhTX-444 (7), and PhTX-333 (8)], each having four protolytic sites, were characterized by 13C NMR spectroscopy. Nonlinear, multiparameter, simultaneous fit of all chemical shift data obtained from the NMR titration curves yielded macroscopic pKa values as well as intrinsic chemical shift data of all differently protonated macrospecies. Analyses of the chemical shift data demonstrated strong interactions between all four sites and provided information about complex relationships between chemical shift values and protonation state. Deprotonation of fully protonated forms starts at the central amino group of the polyamine moiety, and the extent of this trend depends on the distance to the flanking, protonated amino groups. The pKa1 values of 1-8 are in the range 8.2-9.4. Hence, some of the toxins are incompletely protonated at the pH and ionic strength conditions used for assessment of their interactions with ionotropic glutamate and nicotinic acetylcholine receptors, and the degree of protonation is expected to have pharmacological importance in the ion-channel binding event.
KW - Animals
KW - Carbon
KW - Carbon Isotopes
KW - Magnetic Resonance Spectroscopy
KW - Molecular Structure
KW - Polyamines
KW - Titrimetry
KW - Wasp Venoms
KW - Wasps
U2 - 10.1002/mrc.1890
DO - 10.1002/mrc.1890
M3 - Journal article
C2 - 16941578
VL - 44
SP - 1013
EP - 1022
JO - Magnetic Resonance in Chemistry
JF - Magnetic Resonance in Chemistry
SN - 0749-1581
IS - 11
ER -
ID: 42346259