Solution Properties and Potential Biological Applications of Zwitterionic Poly(ε-N-methacryloyl-l-lysine)

Abstract

Poly(ε-N-methacryloyl-L-lysine) (PMALys) was synthesized by free radical polymerization yielding a zwitterionic polymer with M w = 721 000 g mol −1 . The polymer dissolves in pure water as well as in aqueous salt solution up to 5 M NaClO 4 and over wide range of pH values (1.3 ≤ pH ≤ 12.7) as single chains without any sign for aggregate formation. The zwitterionic polymer shows an expanded random coil structure at and close to isoelectric conditions and further expands upon addition of acid and base, respectively. The polymer fulfills four major prerequisites for a promising nano carrier in potential biomedical applications: (1) It is biocompatible, indicated by a low cytotoxicity. (2) It does not aggregate in concentrated human blood serum solution. (3) The amino groups in the polyzwitterion may be utilized for conjugations as demonstrated by labeling reactions with AlexaFluor488. (4) Cell uptake experiments revealed little uptake in bone marrow dendritic cells, i.e., little unspecif ic uptake, which is mandatory for a successful specific targeting of cells. Finally, upon addition of Zn 2+ ions the polyzwitterions may be converted into polycations which are demonstrated to form complexes with DNA. Such complexes may be advantageous for application in gene transfection studies.

Dual-Stimuli-Responsive l-Serine-Based Zwitterionic UCST-Type Polymer with Tunable Thermosensitivity

“…The observed higher molecular weights may be the result of coiled structure of the zwitterionic PSAs in aqueous solution or may be due to the effect of CTA at that reaction conditions. 25,39 The exact reason for this discrepancy in molecular weights is under investigation in our laboratory. At this point, we could only say that PSA of low PDIs can be synthesized via the RAFT polymerization technique.…”

“…Accordingly, three different molecular weights of PSAs were synthesized (see Table 1 It is usually difficult to measure molecular weights of the zwitterionic polymers via GPC because of their significant interaction with the column materials and the high tendency of association of polymer chains in water. 13,25 To avoid this problem, we used 0.1 M LiBr aqueous solution as an eluent to measure the molecular weight of PSA. Figure 1 shows the unimodal GPC traces of three PSA samples.…”

“…11,18,24,25 In addition to this, poly(sulfobetaine) with tunable UCST has been extensively reported by several researchers. 26−29 Chang et al have also studied reversible pH-and salt-responsive soluble−insoluble phase transition in detail for the zwitterionic poly(sulfobetaine methacrylate)s. 30,31 Recently, Agarwal and co-workers published an excellent review focused on detailed discussion on polymers with UCST-type transition in aqueous solution.…”

Amino Acid Functional Polymers: Biomimetic Polymer Design Enabling Catalysis, Chiral Materials, and Drug Delivery

“…The copper is easily removed with 8-hydroxyquinoline, which has higher binding affinity for the metal ion. This strategy (Scheme 4), based on Kurtz's work in 1941, [26] has been used to synthesize methacrylate monomers made from lysine, [27][28][29] serine, [30] tyrosine, orthinine, [25,31] and hydroxyproline. [32] Thia-Michael addition chemistry has been used by the groups of Leggett and Armes to synthesize a zwitterionic monomer from methacrylate-acrylate precursor (3-acryloxy)-2-hydroxypropyl methacrylate) and cysteine (Scheme 5).…”

“…Amidation [35] Acylation [29,31,46] A Thermal responses are often added with amide groups, with the coupling of hydrophobic groups to this polar bond. The addition of an amide does not mean that a temperature response will be added to resulting polymer.…”