TY - JOUR
T1 - Chemical synthesis and biological activities of 3-alkyl pyridinium polymeric analogues of marine toxins
AU - Houssen, Wael E.
AU - Lu, Zhibao
AU - Edrada-Ebel, Ruangelie
AU - Chatzi, Christina
AU - Tucker, Steven J.
AU - Sepčić, Kristina
AU - Turk, Tom
AU - Zovko, Ana
AU - Shen, Sanbing
AU - Mancini, Ines
AU - Scott, Roderick H.
AU - Jaspars, Marcel
N1 - Funding Information:
Acknowledgements This work was supported by a grant fund from NESTech. WH would like to thank R. Yücel and L. Duncan of the flow cytometry core facility at University of Aberdeen for the training on the FACS machines. Authors would also like to thank L. Ford of the Institute of Medical Sciences, University of Aberdeen for providing the HEK 293 cells. MJ is the recipient of a BBSRC Research Development Fellowship. KS, TT and AZ wish to thank the Slovenian Research Agency for the financial support.
PY - 2010/8
Y1 - 2010/8
N2 - Two new large poly-1,3-dodecylpyridinium salts, APS12 and APS12-2 of 12.5- and 14.7-kDa size, respectively, were synthesised and tested for their pore-forming and transfection capabilities in HEK 293 and undifferentiated mouse ES cells using patch-clamp recording, Ca2+ imaging and flow cytometry. Polymerisation reactions were enhanced by microwaves, and the product sizes were controlled by altering the irradiation time. This method can also be applied to obtain polymers with variable linking chains as shown by the preparation of poly-(1,3-octylpyridinium) salt of 11.9-kDa size. Molecular weights of the final products were determined using ESIMS analysis, which also indicated the products to be amongst the largest macro-cycles ever recorded, up to a 900-membered ring. Anti-bacterial, haemolytic and anti-acetylcholinesterase activities were also reported for the two dodecyl pyridinium polymers. These biological activities are characteristic to the structurally related marine toxin, poly-APS.
AB - Two new large poly-1,3-dodecylpyridinium salts, APS12 and APS12-2 of 12.5- and 14.7-kDa size, respectively, were synthesised and tested for their pore-forming and transfection capabilities in HEK 293 and undifferentiated mouse ES cells using patch-clamp recording, Ca2+ imaging and flow cytometry. Polymerisation reactions were enhanced by microwaves, and the product sizes were controlled by altering the irradiation time. This method can also be applied to obtain polymers with variable linking chains as shown by the preparation of poly-(1,3-octylpyridinium) salt of 11.9-kDa size. Molecular weights of the final products were determined using ESIMS analysis, which also indicated the products to be amongst the largest macro-cycles ever recorded, up to a 900-membered ring. Anti-bacterial, haemolytic and anti-acetylcholinesterase activities were also reported for the two dodecyl pyridinium polymers. These biological activities are characteristic to the structurally related marine toxin, poly-APS.
KW - Marine toxins
KW - Microwave-assisted polymerisation
KW - Poly-APS
KW - Pore formers
KW - Transfection
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U2 - 10.1007/s12154-010-0036-4
DO - 10.1007/s12154-010-0036-4
M3 - Article
C2 - 21326630
AN - SCOPUS:77955517182
SN - 1864-6158
VL - 3
SP - 113
EP - 125
JO - Journal of Chemical Biology
JF - Journal of Chemical Biology
IS - 3
ER -