Determining Sequence Fidelity in Repeating Sequence Poly(lactic-co-glycolic acid)s

Abstract

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.

Precision Aliphatic Polyesters with Alternating Microstructures via Cross‐Metathesis Polymerization: An Event of Sequence Control

“…On the other hand, periodic sequences of HP1 and HP2 were further characterized by MALDI‐TOF‐MS spectra as shown in Figure . A myriad of peaks with regular intervals that are equal to the theoretical repeating unit mass were observed in each of these spectra, suggesting the integrity of microstructural periodicity . Furthermore, minor series of peaks deviating from major series by several methylene units owing to olefin isomerization were not detectable, confirming the excellent capability of inhibitor BQ in preventing this side reaction.…”

Closed-Loop Polymer Upcycling by Installing Property-Enhancing Comonomer Sequences and Recyclability

“…Copolymerizing two or more monomers is a well-established strategy to create new copolymer materials that often deliver unattainable or improved properties over those of homopolymers. − By adjusting the comonomer chemical nature, sequence, stereochemistry, and the composition, the properties and functions of the resultant copolymers can be tailored in a wide range to meet the desired application demand. − A notable example in this context is poly­(lactide- co -glycolide) (PLGA), − which was approved by FDA for biomedical applications and shows improved flexibility, processability, and degradation behavior, relative to homopolymer poly­(glycolic acid) (PGA), since PGA’s melting-transition temperature ( T m ) of ∼219 °C is close to its onset thermal decomposition temperature ( T d ) of ∼250 °C, and its dissolvability in common organic solvents is extremely poor. , Nevertheless, the resulting PLGA is still a rather brittle material (∼6% elongation at break).…”

Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry of model prebiotic peptides: Optimization of sample preparation

“…The latter reason is intentional, as it is thought neither arginine nor lysine was prebiotically available . The use of a cation source instead of a proton source is common in polymer MALDI, and was recently used for polyesters similar to our depsipeptides which contained lactic acid (a) and glycolic acid (g) residues …”