Chemical conjugation of cowpea mosaic viruses with reactive HPMA-based polymers.
N-(2-Hydroxypropyl)methacrylamide (HPMA) co-polymers containing disulfide and carbonyl thiazolidine-2-thione (TT) reactive groups in their side-chains (pHPMA-TT) were used as reductively removable chemical modification of the surface of cowpea mosaic viruses (CPMV). CPMV was used in this study as a model particle for viral gene delivery. The co-polymer reaction with CPMV surfaces carried out in aqueous solution was evaluated by monitoring the changes in the weight-average molecular weight and hydrodynamic size of the viruses using light scattering methods. The reaction conditions were optimized. The surface modification of CPMV with pHPMA-TT under selected conditions (concentrations of a coating polymer (c(p)) and NaCl) has not influenced the size distribution of the viral particles. The uncharged polymers bound to the viral surface via biodegradable S-S bonds can be fully removed by the exchange reaction with reductive dithiothreitol. To achieve optimal covering of viral surfaces, the positively charged reactive polymers (with or without biodegradable S-S bonds) should be applied at low concentrations (c(p)=0.1-0.5 mg/ml) and in presence of NaCl (0.15 M).
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Square 2, 16206 Prague 6, Czech Republic. laga@imc.cas.cz
Richard
R
Laga
Cestmír
C
Konák
Vladimír
V
Subr
Karel
K
Ulbrich
Nisaraporn
N
Suthiwangcharoen
Zhongwei
Z
Niu
Qian
Q
Wang
D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D032701:Biomimetics; D017798:Comovirus / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism; D008689:Methacrylates / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties; D053778:Thiazolidines / Q000737:chemistry
D001672:Biocompatible Materials; D004220:Disulfides; D008689:Methacrylates; D011108:Polymers; D053778:Thiazolidines; C005104:2-mercaptothiazoline; C032802:hydroxypropyl methacrylate