![A phosphorylation rate expressed as the yield (Y) of -[32P]ATP
produced by 1 mg of pure enzyme per 1 min related to the ATP synthesis
rate (Y0) directed by enzyme sample with a natural abundance of Mg2+
isotopes as a function of 25Mg content in CK active sites.](https://image.slidesharecdn.com/random-110601093348-phpapp01/85/-8-320.jpg)
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кузнецов
- 1. A NOVEL FAMILY OF MEDICINAL NANOPARTICLES TO PROMOTE THE MAGNETIC ISOTOPE EFFECT FOR PHARMACOLOGICAL PURPOSES Dmitry A. Kuznetsov Vladimir P. Chekhonin N.N. Semenov Institute for Chemical Physics, Russian Academy of Sciences, Moscow, Russia Department of Medicinal Nanobiotechnology, N.I. Pirogov Russian State Medical University, Moscow, Russia
- 2. THE CREATINE KINASE ACTIVE SITE NANOTOPOLOGY
- 4. The rate of ATP formation by mitochondria (A) and by creatine kinase (B) as a function of magnesium isotope intact mitochondria mitochondria subjected to a selective blockade of oxidative phosphorylation by 1-methylnicotine amide. A B 25 1.0 24 26 The yield of ATP is given in mmole/g total protein
- 5. ION – RADICAL PAIRS FORMATION (SINGLET – TRIPLET PATH SHIFT) MECHANISM OF THE 25Mg MAGNETIC ISOTOPE EFFECT EXPRESSED IN A BIOLOGICAL PHOSPHORYLATION PRECESSES (Mt-CK)
- 6. THE CK CATALYTIC SITE NANOTOPOLOGY IMPACT ONTO THE REAGENTS ELECTRON DENSITY OVERLAP A combined systemic solution of both Schroedinger and Poissone equations processed
- 7. The GPK reaction ion-radical mechanism
- 8. A phosphorylation rate expressed as the yield (Y) of -[32P]ATP produced by 1 mg of pure enzyme per 1 min related to the ATP synthesis rate (Y0) directed by enzyme sample with a natural abundance of Mg2+ isotopes as a function of 25Mg content in CK active sites.
- 9. Buckminsterfullerene(C60)-2-(butadiene-1-yl)- -tetra(o--aminobutyryl-o-phtalyl)porphyrin PORPHYLLERENE – MC16 COO- -OOC CH2 CH2 HC NH2 2+ H N 2 CH H2C COO- 2 Mg -OOC CH2 COO- -OOC N N Fe N N COO- -OOC COO- -OOC CH2 CH2 HC NH2 H2N CH 2+ CH2 2 Mg CH2 COO- -OOC
- 10. PMC16 CATIONITE PROPERTIES AND THE NANOCLUSTERS FORMATION AS A FUNCTION OF pH 14.8nm 10.2nm 6.4nm 4.7nm 3.2nm 1.15nm pH Blue arrow shows the iron-dextrane sphere exclusion limit Blue arrow shows the iron-dextrane sphere exclusion limit , portion of the total PMC16 magnesium
- 11. THE EFFECT OF A PMC16 – TARGETED DELIVERY OF Mg2+ ON THE DOXORUBICIN (DXR) PRE – SUPPRESSED ATP PRODUCTION IN RAT MYOCARDIUM 0.8 DL50 DXR, i.v., 6 hrs → PMC16, i.v., 6 hrs
- 12. SYNERGISM OF THE MITOCHONDRIAL MATRIX CK ACTIVITY, MAGNESIUM CATIONS INFLUX AND THE FREE PROTONS EXCESS DEGREE CK Relative Activity The isolated rat myocardium mitochondria tested. Yellow / Red stands for the spinless / spin Mg isotopes ratio.
- 13. SYNERGISM OF THE ATP YIELD, OXYGEN CONSUMPTION AND THE Mg2+ INFLUX IN THE PERFUSED ISOLATED RABBIT HEART MUSCLE TISSUE A B ATP yield, Y/Yo ATP yield, Y/Yo A – Zero spin magnesium test B – Magnetic magnesium test
- 19. ELECTRON TRANSMITTING MICROPHOTOGRAMS OF THE RAT MYOCARDIOCYTIC PERINUCLEAR AREAS A B D C A, C – PMC16 related hypoxia preventing effect B – Inhalation oxygen deficiency hypoxia model D – Intact myocardium
- 20. PMC16 CLUSTER POSITIONING INSIDE THE RAT MYOCARDIOCYTIC MITOCHONDRIAL MEMBRANE IN METABOLIC ACIDOSIS (a, c) AND IN NORMAL CONDITIONS (b, d) a, b – Laser contrast (Nanofinder-S-6A) images C, d – Confocal scanning microscopy
- 21. PMC16 nanoclusters immobilized on acetyl cellulose membrane a – LCM, pH 7.00 b – LCM, pH 8.40 c – AFM, pH 8.80
- 22. A HIGHLY SELECTIVE TRAGETING OF PMC16 NANOPARTICELS TOWARDS THE RAT HEART MUSCLE IN A COURSE OF THE LONG – TERM ADMINISTRATION OF AN EXTRA LOW DRUG DOSAGE
- 23. NOTE: DXR, 20 mg/kg/24 hrs, i.v.: MNA, 10 mg/kg/24 hrs, i.v.:
- 26. CONCLUSIONS PORPHYRINE ADDUCTS OF FULLERENE C60, A NEW FAMILY OF MEDICINAL NANOPARTICLES TO MEET THE FOLLOWING EXPECTATIONS: • Tissue-selective targeted delivery of 25Mg2+ paramagnetics to the porphyrin-signaling cell compartments in myocardium and, to a lesser degree, lymphocytes • The 25Mg2+-related magnetic isotope effect to promote a local and fast, jump-up increase of ATP production, even in the tissue oxygen deplete of any sort • Smart nanoparticles behavior while in Mt-membrane, i.e. a gradual 25Mg2+ release that occurs exclusively in response to the tissue hypoxia-caused metabolic acidosis • Low toxic, safe, efficient and completely eliminable (C60- clearing / porphyrin metabolizing) agents, all suitable for either short or long term administration schemes