Spermine

These compounds are present in almost all mam malian cells where they are believed to be involved in cell differentiation and proliferation Because each ni trogen of a polyamine is protonated at physiological pH (7 4) putrescine spermidine and spermine exist as cations with a charge of + 2 +3 and + 4 respectively... 

Polyamine (Section 22 4) A compound that contains many ammo groups The term is usually applied to a group of nat urally occurring substances including spermine spermi dine and putrescme that are believed to be involved in cell differentiation and proliferation Polycyclic aromatic hydrocarbon (Section 118) An aromatic hydrocarbon charactenzed by the presence of two or more fused benzene rings... 

Spermine 4HC1 (7V,7V-bis(3-aminopropyl)-l,4-butanediamine 4HC1) [306-67-2] M 348.2, m 313-315". The pKs are similar to spermidine above. Purification as for spermidine trihydrochloride above. 

Fig. 20. Schematic representation of the unrolled major groove of the MPD 7 helix showing the first hydration shell, consisting of all solvent molecules that are directly associated with base edge N and O atoms. Base atoms are labeled N4,04, N6,06 and N7 solvent peaks are numbered. Interatomic distances are given in Aup to 3,5 A represented by unbroken lines, between 3,5-4,1 A by dotted lines. The eight circles connected by double-lines represent the image of a spermine molecule bound to phosphate groups P2 and P22. There are 20 solvent molecules in a first hydration layer associated with N- and O-atoms l58)...

In addition, the linear, biogenic polyamines, spermidine and spermine, originally isolated from human sperm19), have been long known. Their structures are shown below. 

Cyclic spermine) (Cyclic spermine) ICyclic spermine)... 

At pH 7, [13]aneN3 or [12]-[15]aneN4 accommodate only two nitrogen-bound protons and these dipositive ammonium cations are apparently unable to provide sufficient electrostatic attraction to polycarboxylate anions for ion-pair formation. In contrast, the macrocyclic spermines, pentaamines and hexaamines accommodate more than three nitrogen-bound protons at pH 7 and for these ligands 1 1 associations... 

The conditional association constant for [18]aneN4 ( cyclic spermine ) with ATP - at pH 7.5 is calculated from the (3L value (Table 5) and protonation constants (Table 1) to be 2.4x 105 M-1, which is larger than the association constants for the linear spermidine (9 xi 02 M ) and spermine (9.5 x 103 M-1)23). It is also of interest that cyclic spermine is selective for ATP over AMP (ratio association constants is 700), while linear spermine prefers ATP to AMP only by a ratio of 26 to 1 43). The selective complexation of biologically important anions is of particular interest, especially if the ligands are converted into selective anion carriers by attachment of lipophilic hydrocarbon chains. 

Eflornithine (difluoromethylornithine, DFMO) inhibits the ornithine decarboxylase of the polyamine pathway, in both the trypanosome and the mammalian cell, by acting as an irreversible competitor of the natural substrate ornithine. Inhibition of ornithine decarboxylase results in depletion of the polyamines, putrescine, spermidine and spermine, which are essential for cell proliferation. Eflornithine selectively harms the parasite and not the mammalian cells, despite acting as an ornithine decarboxylase inhibitor in both cell types. This selectivity is explained by the lower rate of ornithine decarboxylase production in the parasite, as compared to mammalian cells. Due to the high turnover rate, mammalian cells are capable of quickly replenishing inhibited ornithine decarboxylase by newly... 

Lovinger DM (2000) Examination of ethanol spermine and acamprosate actions on native and recombinant NMDA receptors. Alcohol Clin Exp Res 24 183A... 

Inward Rectifier K+ Channels. Figure 5 Proposed three-dimensional arrangement of the transmembrane region of Kir channels. Two of four subunits are indicated. The pore consists of a selectivity filter close to the outside part of the membrane, a central inner vestibule, and a cytoplasmic entrance. Spermine may block in the inner cavity or in the selectivity filter. Large intracellular vestibule where polyamines may also block the channel is not shown. 

Inward Rectifier K+ Channels. Figure 6 Spermine (Amino-propyl-amino-butyl-amino-propyl amine) is a long linear naturally occurring polyamine containing four nearly equally spaced positively charged (at normal pH) amines. Although 16 A long, the molecule is only about 3 A wide, similar to a dehydrated potassium ion. 

Spermine is one of the most common natural polyamines in eukaryotes with the following structure NH2(CH2)3NH(CH2)4NH(CH2)3NH2. 

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