Dual Responsiveness of a Tunable Thermosensitive Polypeptide

Abstract

The temperature and pH dependent solubility of poly(γ-propargyl L-glutamate) (PPLG) functionalized through copper catalyzed 1,3 cycloaddition reaction between an alkyne and azide can be tuned with precision over a broad range of conditions by varying the ratio of substitution of short oligo ethylene glycol and diisopropylamine side groups.

Role of Side-Chain Molecular Features in Tuning Lower Critical Solution Temperatures (LCSTs) of Oligoethylene Glycol Modified Polypeptides

“…8 Initial efforts in this area focused on polymethacrylates and polyacrylates containing OEG side-chain groups, [9][10][11][12] and now this motif has been used to prepare other types of thermoresponsive polymers, such as OEG containing polypeptides. [13][14][15][16][17][18][19][20][21][22][23] Thermoresponsive polypeptides are desirable compared to other polymers since they can degrade in living systems, which is advantageous for biological and medical applications. OEG containing thermoresponsive polypeptides have been prepared using a variety of methods, using different core amino acid residues, and also with a wide range in number of ethylene glycol (EG) repeats and means of their attachment to different residues.…”

“…OEG containing thermoresponsive polypeptides have been prepared using a variety of methods, using different core amino acid residues, and also with a wide range in number of ethylene glycol (EG) repeats and means of their attachment to different residues. [13][14][15][16][17][18][19][20][21][22][23] While many thermoresponsive polypeptides have been described that possess LCSTs, there is limited understanding of how the molecular features of different side-chain structures affect solution properties. For most thermoresponsive polypeptides, LCST is mainly adjusted by variation of the number of side-chain EG repeats, with less attention given to the components of different linkages.…”

“…For most thermoresponsive polypeptides, LCST is mainly adjusted by variation of the number of side-chain EG repeats, with less attention given to the components of different linkages. [13][14][15][16][17][18][19][20][21][22][23] Hence, it can be difficult to understand the differences in thermoresponsive properties of OEG containing polypeptides prepared using different amino acids and side-chain linkages. Here, we have utilized a recently developed synthetic methodology that allows facile modification of polypeptide sidechains 24,25 to prepare a series of thermoresponsive OEG containing polypeptides, where the number of EG repeats, EG terminal groups, and linkage groups were all systematically varied in order to obtain insights on how these molecular features affect LCST behavior ( Figure 1).…”

“…All of the non-ionic OEG-Hcy samples described above were found to adopt predominantly α-helical conformations in deionized water at 22 °C (except for water insoluble 2c, which was measured in MeOH at 22 °C), as determined by circular dichroism (CD) spectroscopy (see SI Figure S1) We envisioned that most of these OEG-Hcy derivatives would be thermoresponsive similar to OEG containing polypeptides reported by ourselves and other workers. [13][14][15][16][17][18][19][20][21][22][23] The significance of this new series of polymers is the incorporation of precise side-chain structural modifications, which enable systematic study of the effects of different functionalities on the properties of the materials. Figure 2 shows the results obtained from analysis of aqueous solutions of all the different OEG-Hcy homopolymers at concentrations of 3.0 mg/ml.…”

Stimuli‐responsive polypeptide materials prepared by ring‐opening polymerization of α‐amino acid N‐carboxyanhydrides

“…4(c)]. 53 Besides the above discussed chemistry, amidation of available polymer to form thermo-responsive poly(amino acid)s was also reported in literature. For example, Kobayashi and coworkers 54 prepared a biodegradable thermo-responsive poly(N-hydroxyalkyl-a/b-asparagine) from a reaction of poly(succinimide) with a mixture of 5-aminopentanol and 6-aminohexanol.…”