HYBRID EVENT: You can participate in person at Paris, France or Virtually from your home or work.
Paris, France
September 30 - October 2, 2021

Vakhtang Barbakadze

Speaker for GPMB 2021 - Vakhtang Barbakadze
Vakhtang Barbakadze
Tbilisi State Medical University, Georgia
Title : A new representative of poly(sugar acids): Acidic polysaccharide poly[3-(3,4-dihydroxyphenyl)glyceric acid], its synthetic analogues and potential therapeutic effect

Abstract:

A new polysaccharide is the main chemical constit­uent of  high molecular (>1000 kDa) water-soluble preparations from  medicinal plants of  Symphytum asperum, S.caucasicum, S.officinale, S.grandiflorum,  Anchusa italica, Cynoglossum officinale and  Borago officinalis (Boraginaceae) according to data of liquid-state 1H, 13C NMR, 2D 1H/13C  HSQC, 2D DOSY and solid-state 13C NMR spectra was found to be poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] or poly[3-(3,4-dihydroxyphenyl)glyceric acid] (PDPGA). The polyoxyethylene chain is the backbone of this biopolymer. 3,4-Dihydroxyphenyl  and  carboxyl  groups are  regular  substituents  at  two  carbon  atoms  in the chain with the  3-(3,4-dihydroxyphenyl)glyceric acid  residue as the repeating unit. PDPGA as a 3,4-dihydroxyphenyl derivative of poly(2,3-glyceric acid ether) belongs to a class of an acidic polysaccharides [poly(sugar acids)] as well. Its basic monomeric moiety glyceric acid is oxidative form of the aldotriose glyceraldehyde. In this case poly(2,3-glyceric acid ether) chain is the backbone of this polymer molecule and 3,4-dihydroxyphenyl groups are regular substituents at 3C carbon atoms in the chain. has not been reported. From the chemical viewpoint, the biosynthesis of the rather rare class of natural polyethers that PDPGA belongs to can be conceived as the epoxidation of the double bond in caffeic acid followed by the polymerization of the resulting oxirane. PDPGA as a unique natural polyether contains aliphatic ether groups in its polymer backbone. Naturally occurring ethers include small molecules such as antibiotics, or aromatic polymer such as lignin. Lignin contains ether links between two aromatic rings or between an aromatic ring and an aliphatic moiety. However, reports concerning polymers that contain aliphatic ethers as repeating unit are missed. Every repeating structural unit of PDPGA contains three reactive functional groups, two phenolic hydroxyl groups in ortho-position and one carboxyl group. The structural unit of synthetic polymers poly(1,2-glyceric acid carbonate) and poly(1,2-glycerol carbonate) contain only one reactive carboxyl and one reactive –CH2OH groups, respectively. Overall, multifunctionality of PDPGA should be a reason of its wide spectrum of biological activities. The basic monomeric moiety of PDPGA was synthesized via Sharpless asymmetric dihydroxylation of trans-caffeic acid derivative using a potassium osmate catalyst. Methylated derivative of PDPGA was synthesized via ring opening polymerization (ROP) of 2-methoxycarbonyl-3-(3,4-dimethoxyphenyl)oxirane using a cationic initiator BF3·OEt2. Oligomers of PDPGA was  synthesized  by “green” ROP enzymatic polymerization of methyl 3-(3,4-dibenzyloxyphenyl)glycidate using lipase from Candida rugosa. Enzymatically obtained oligomers of natural polyether cause interest for diverse biological tests. Human Hyaluronidase (Hyal-1) degrades high molecular mass Hyaluronic acid (HA) into smaller fragments which have pro-inflammatory effects. PDPGA possesses the ability to inhibit the enzymatic activity of Hyal-1 completely. Consequently, PDPGA exhibited anti-inflammatory efficacy. PDPGA and its synthetic monomer exerted anticancer activity in vitro and in vivo against androgen-dependent  and -independent  human prostate cancer (PCA) cells via  targeting  androgen  receptor, cell  cycle  arrest  and  apoptosis  without  any toxicity, together  with  a strong  decrease  in  prostate specific antigen level in plasma. The anticancer efficacy of PDPGA against human PCA cells is more compared to its synthetic monomer. Methylated PDPGA did not show any activity against PCA. Thus, PDPGA was identified as a potent agent against PCA without any toxicity.

Biography:

Vakhtang Barbakadze has his expertise in isolation and structure elucidation of  biologically active plant polysaccharides and polyethers. In 1978 and 1999 he has completed his Ph.D and D.Sci., respectively. He is the Head of Department of Plant Biopolymers at the Tbilisi State Medical University Institute of Pharmacochemistry. In 1996 and 2002 he has been a visiting scientist at Utrecht University (The Netherlands) by University Scholarship and The Netherlands organization for scientific research (NWO) Scholarship Scientific Program, respectively. He has published more than 100 papers in reputed journals. In 2004 he was Georgian State Prize Winner in Science and Technology.

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