A Systematic Study on the Self-Assembly Behaviour of Multi Component Fmoc-Amino Acid-Poly(oxazoline) Systems

Abstract

Abstract:We report a systematic study of a modular approach to create multi-component supramolecular nanostructures that can be tailored to be both enzyme and temperature responsive. Using a straightforward synthetic approach we functionalised a thermal responsive polymer, poly(2-isopropyl-2-oxazoline), with fluorenylmethoxycarbonyl-amino acids that drive the self-assembly. Depending on the properties of appended amino acids, these polymers undergo substantial morphological changes in response to the catalytic action of alkaline phosphatase.

Fmoc-modified amino acids and short peptides: simple bio-inspired building blocks for the fabrication of functional materials

“…Such gels can be employed as ideal low-molecular-weight hydrogelators, as shown in Table 1. [29][30][31][32][33] Of note is Fmoc-F, which is a leading hydrogelation promoter due to its excellent propensity to self-assemble. 29 Other amino acids are mostly the derivatives of Fmoc-F, such as its fluorinated 30 and hydroxylated (Fmoc-Y 29,31,33 and its phosphorylated derivatives, 31,33 Fmoc-DOPA 32,34 ) derivatives.…”

“…51 Besides, conjugation of poly(2-isopropyl-2oxazoline) (PiPrOx), a thermoresponsive polymer, to Fmocmodified amino acids could provide several Fmoc-amino acid-PiPrOx molecules which self-assemble to form temperatureresponsive colloidal particles. 33 By increasing the temperature from room temperature to above the lower critical solution temperature (LCST), a phase transition from the solution phase of these conjugates to precipitates could be induced. 33 Moreover, the types of amino acids, such as Fmoc-F or Fmoc-Y, could drastically influence the self-assembly behaviors.…”

Poly(2-oxazoline)s and click chemistry: A versatile toolbox toward multi-functional polymers

“…Similar temperature-induced alterations of the morphology were observed for CuAAC clicked PEtOx-peptide bioconjugates that self-assembled into nanotubes below the LCST and hydrophobic microspheres above the LCST. 38 Conjugates of PiPropOx and fluorenylmethoxycarbonyl-amino acids, prepared using CuAAC click chemistry, formed colloidal particles depending on the type of amino acid attached, as shown by Caponi et al 37 Moreover, two component mixtures of these colloidal systems and a phosphate functionalized iPropOx-amino acid, showed additional enzyme responsive behavior upon addition of phosphatase, which alters the amino acid charge and functionality by transforming the phosphate moiety to a hydroxyl group. Other, non-spherical nanostructures, were reported by Schacher et al for self-assembling oligophenyleneethynylenes (OPE)-PEtOx bolaamphiphiles.…”

“…It must be noted that the acetylene group is susceptible to deprotonation and side reactions can occur upon termination with methanolic potassium hydroxide, which is a commonly used terminating agent for the CROP of 2-oxazolines. 34 The commercial availability of propargyl tosylate and the efficiency of the CuAAC click conjugation, made this route towards clickable PAOx very popular and many functionalities, including virus-like particles, 35 thermo-responsive dendrimers, 36 amino acids, 37 and cyclic peptides 38 have been coupled in a similar way (cfr. section 2.2).…”

Stimuli-Responsive Polymers Providing New Opportunities for Various Applications

“…The behavior of self-assembly [407,408] and disassemble [376,383,384] is obtained by the change in hydrophilicity of one block of a block copolymer (Figure 10f). In addition to this behavior observed in micelles, changes occur in micelle morphologies due to their enzyme-sensitive natures (Figure 10g) [355,[409][410][411][412][413][414][415][416][417][418]. Additionally, enzyme-responsive surfaces can be produced for different purposes [419][420][421][422] (Figure 10h and 10i).…”