Conformations of Spermine in Adenosine Triphosphate Complex: The Structural Basis for Weak Bimolecular Interactions of Major Cellular Electrolytes

Abstract

Selectively (2)H- and (13)C-labeled spermines (SPM) were efficiently synthesized and analyzed by NMR spectroscopy to determine the spin-spin coupling constants for six conformationally relevant bonds. SPM that is composed of three alkyl moieties, a butanylene, and two propanylene chains undergoes a conformational change when interacting with multivalent anions (e.g., adenosine triphosphate (ATP), ATP-Mg(2+) , and tripolyphosphate). Upon interaction with ATP, the C-C bonds, which affect the distance between the neighboring pairs of ammonium groups (i.e., N1/N5 and N5/N5'), increase the population of gauche rotamers by 17-20% relative to those in the 4 HCl salt of SPM. However, the trend in increments of the gauche conformers for the SPM-ATP complex profoundly differs from that of the spermidine (SPD)-ATP complex. This implies that SPM may preferentially recognize the adenyl group of ATP rather than the tripolyphosphate moiety. This may account for the higher affinity of SPM to ATP-Mg(2+) than with that of SPD, which chiefly interacts with β- and γ-phosphates and is easily replaced by Mg(2+) . These results may provide a clue for the further understanding of the structural basis of polyamine biological functions.

Schiff base formation and recognition of amino sugars, aminoglycosides and biological polyamines by 2-formyl phenylboronic acid in aqueous solution

“…However, it has been shown by NMR studies of specifically 2 H-labeled spermines that contact with an anion induces strong increase in fraction of gauche rotamers around C2-C3, C3-C4 and C6-C7 bonds so that the polycation can essentially wrap the anionic species. 34 To confirm this possibility we performed a M06-HF/6-31G(**) 35 level quantum mechanical calculation taking into account solvation in water of the structure of imine formed with the terminal amino group of the triply protonated spermine, Fig. 10.…”

Insight into the molecular recognition of spermine by DNA quadruplexes from an NMR study of the association of spermine with the thrombin‐binding aptamer

“…The NOE between the α2″ and the β methylenes of free spermine is much weaker than the other NOEs reflecting the long internuclear distance between these methylenes in the predominant extended conformation (Figure A). The population of the trans conformers in free spermine at neutral pH is estimated to be greater than 75% (Maruyoshi et al ., ). In contrast, the corresponding α2″–β NOE in TBA‐bound spermine has increased relative to the α2″–γ NOE (Figure B).…”

“…In contrast, a substantial α2″–β NOE and the presence of a γ–β NOE in TBA‐bound spermine are inconsistent with the long internuclear distances of the extended conformation. Spermine assumes a more compact conformation by increasing the population of gauche rotamers at certain bonds (Egli et al ., ; Bancroft et al ., ; Maruyoshi et al ., ), resulting in a reduction in the distance between the ammonium groups. This is particularly true of the central aminobutyl segment, which has a larger N–N internuclear distance than the nitrogen atoms that enclose the outer aminopropyl segments.…”