Lysine-containing polymers have seen broad application due to their amines' inherent ability to bind to a range of biologically relevant molecules. The synthesis of multiple generations of polyester dendrimers bearing lysine groups on their periphery is described in this report. Their hydrolytic stabilities with respect to pH and time, their toxicity to a range of cell lines, and their possible application as nano-detoxification agents of organophosphate compounds are all investigated. These zeroth-, first-, and second-generation water-soluble dendrimers have been designed to bear exactly 4, 8, and 16 lysine groups, respectively, on their dendritic periphery. Such monodisperse bioactive polymers show potential for a range of applications including drug delivery, gene delivery, heavy metal binding, and the sequestration of organic toxins. These monodisperse bioactive dendrimers were synthesized using an aliphatic ester dendritic core (prepared from pentaerythritol) and protected amino acid moieties. This library of lysine-conjugated dendrimers showed the ability to efficiently capture the pesticide dichlorvos, confirming the potential of dendrimer-based antidotes to maintain acetylcholinesterase activity in response to poisoning events.

The synthesis and characterization of sequenced copolymers is a relatively underdeveloped field despite the fact that biological polymer properties are known to depend directly on sequence. The concept of sequence fidelity is introduced and defined for repeating sequence copolymers as the ratio of repeat units of the target sequence to the total number of repeat units. 1 H NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI−ToF MS) are used to characterize the sequence fidelity of repeating sequenced copolymers comprising poly(lactic-co-glycolic acid)s. Both characterization methods are found to have both advantages and weaknesses with regard to identifying and quantifying error in these copolymers. A method for using routine MALDI−ToF MS data to quantify sequence fidelity is proposed and applied to a series of copolymers with synthetically defined error rates. The MS-determined sequence fidelities are comparable to those obtained by NMR analysis.

Calibrants based on synthetic dendrimers have been recently proposed as a versatile alternative to peptides and proteins for both MALDI and ESI mass spectrometry calibration. Because of their modular synthetic platform, dendrimer calibrants are particularly amenable to tailoring for specific applications. Utilizing this versatility, a set of dendrimers has been designed as an internal calibrant with a tailored mass defect to differentiate them from the majority of natural peptide analytes. This was achieved by incorporating a tris-iodinated aromatic core as an initiator for the dendrimer synthesis, thereby affording multiple calibration points (m/z range 600-2300) with an optimized mass-defect offset relative to all peptides composed of the 20 most common proteinogenic amino acids. Graphical abstract ᅟ.

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