Tuning the Viscoelasticity of Peptide Vesicles by Adjusting Hydrophobic Helical Blocks Comprising Amphiphilic Polypeptides

Abstract

Amphiphilic block polypeptides of poly(sarcosine)-b-(l-Val-Aib) and poly(sarcosine)-b-(l-Leu-Aib) and their stereoisomers were self-assembled in water. Three kinds of binary systems of poly(sarcosine)-b-(l-Leu-Aib) with poly(sarcosine)-b-poly(d-Leu-Aib), poly(sarcosine)-b-poly(l-Val-Aib), or poly(sarcosine)-b-(d-Val-Aib) generated vesicles of ca. 200 nm diameter. The viscoelasticity of the vesicle membranes was evaluated by the nanoindentation method using AFM in water. The elasticity of the poly(sarcosine)-b-(l-Leu-Aib)/poly(sarcosine)-b-poly(d-Leu-Aib) vesicle was 11-fold higher than that of the egg yolk liposome but decreased in combinations of the Leu- and Val-based amphiphilic polypeptides. The membrane elasticity is found to be adjustable by a suitable combination of helical blocks in terms of stereocomplex formation and the interdigitation of side chains among helices in the molecular assemblies.

Thermoresponsive polysarcosine-based nanoparticles

“…7 The precise control over PSar synthesis has enabled the accurate synthesis of block copolymers that contain PSar conjugated to other polypeptoids, [8][9][10] poly(ε-caprolactone), 11,12 tertiary aminecontaining molecules, 13 PEG, 14 and poly(amino acids)/polyamides. [15][16][17] There has been much recent interest in the application of PSar for the controlled release of therapeutic compounds. In such instances, PSar habitually forms the hydrophilic, and nonfouling, section of an amphiphilic block copolymer capable of forming nanoparticles in aqueous solution.…”

Tubular Assembly Formation Induced by Leucine Alignment along the Hydrophobic Helix of Amphiphilic Polypeptides

“…The amphiphilic polypeptides PSar 28 - b -( l -Leu-Aib) 6 (S28L12) and PSar 27 - b -( l -Leu-Aib) 8 (S27L16) were synthesized as reported previously [ 21 , 22 , 25 , 27 ]. The amphiphilic polypeptides PSar 24 - b -( l -Leu-Aib) 2 -( l -Ala-Aib) 2 -( l -Leu-Aib) 2 (S24L4A4L4) and PSar 26 - b -( l -Ala-Aib)-( l -Leu-Aib) 6 -( l -Ala-Aib) (S26A2L12A2) were synthesized by modifying a reported synthesis scheme [ 21 , 22 , 24 , 27 ] ( Schemes S1 and S2 ). Briefly, dipeptide units of Leu-Aib and Ala-Aib were synthesized with traditional condensation, and the 12 and 16 mer hydrophobic peptide was obtained by combining their units with sequential liquid-phase synthesis.…”

“…The phenomenon was explained by the hypothesis that the helical part is uniformly packed in a hydrophobic layer due to the concave–convex interaction between helices with the LxxxLxxxL sequence [ 20 , 21 , 22 , 23 ]. Kimura and coworkers demonstrated that PSar n - b -( l -Val-Aib) 6 did not form a nanotube [ 24 ], which showed the importance of the Leu side chain for morphology control. Thus, although soft matter may spontaneously form from amphipathic molecules, its homogeneity and shape design are possible with the precise molecular orientation found in proteins.…”

Poly(sarcosine)-Based Nano-Objects with Multi-Protease Resistance by Aqueous Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA)

“…23 Over the last years, studies on the synthesis and self-assembly behavior of PSar-based block copolymers for the development of nanostructures of biotechnological interest have been presented, although they involve the use of conventional self-assembly procedures in dilute aqueous solutions. 13,23,[27][28][29][30][31][32] Recently, polymerization-induced self-assembly (PISA) has been established as an efficient methodology for facile one-pot fabrication of polymeric nano-objects with predictable morphologies at high solids concentrations (10-50% w/w). [33][34][35][36] Existing limitations of traditional self-assembly strategies (i.e.…”

“…Over the last years, studies on the synthesis and self-assembly behavior of PSar-based block copolymers for the development of nanostructures of biotechnological interest have been presented, although they involve the use of conventional self-assembly procedures in dilute aqueous solutions. ,,− Recently, polymerization-induced self-assembly (PISA) has been established as an efficient methodology for facile one-pot fabrication of polymeric nano-objects with predictable morphologies at high solids concentrations (10–50% w/w). − Existing limitations of traditional self-assembly strategies (i.e., direct dissolution, thin-film hydration, and solvent-switch) such as low polymer concentrations (≤1% w/w) and laborious post-polymerization processing steps for targeting certain morphologies are proven to be overcome by PISA. Only selected monomers have the ability to undergo PISA as a solubility transition of the gradually growing core-forming block from solvent-soluble to solvent-immiscible is required .…”