Peptide‐poly(tert‐butyl methacrylate) conjugate into composite micelles in organic solvents versus peptide‐poly(methacrylic acid) conjugate into spherical and worm‐like micelles in water: Synthesis and self‐assembly

Abstract

Peptide–polymer conjugates are versatile class of biomaterials composed of a peptide block covalently linked with a synthetic polymer block. This report demonstrates the synthesis of peptide‐poly(tert‐butyl methacrylate) (Peptide‐PtBMA) conjugates of varying molecular weights via a “grafting from” atom transfer radical polymerization (ATRP) technique using as‐synthesized peptide‐based initiator in toluene. Peptide‐PtBMA conjugate is soluble in many organic solvents and undergoes self‐assembly into micro/nanospheres in DMF/THF as observed from both FESEM and DLS results. The conjugate micro/nanospheres are nothing but the composite micelles formed by the secondary aggregation of primary micelles generated initially in these organic solvents. The hydrolysis of tert‐butyl groups of Peptide‐PtBMA conjugate leads to the formation of peptide‐poly(methacrylic acid) (Peptide‐PMA) conjugate. The circular dichroism (CD) analysis exhibits the presence of β‐sheet conformation of peptide moiety in synthesized conjugates. The formed Peptide‐PMA conjugate is soluble in water and owing to its amphiphilic character, the conjugate molecules self‐assemble into spherical micelles as well as worm‐like micelles upon increasing the concentration of conjugate in water. However, the sodium salt of Peptide‐PMA conjugates (Peptide‐PMAS) self‐assembles into only spherical swollen micelles in water at higher (pH ∼10). The critical aggregation concentrations (CACs) of both Peptide‐PMA and Peptide‐PMAS micelles are measured by fluorescence spectroscopy. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3019–3031

Peptide‐poly(2‐(dimethylamino)ethyl methacrylate) conjugates: Synthesis and aqueous/nonaqueous self‐aggregation into nanostructures of dendritic and spherical morphologies

“…These spherical nanoparticles are nothing but spherical micelles formed by the self‐assembly of peptide‐PDMAEMA‐I conjugate molecules. However, in this case, we did not observe the formation of large sized composite micelles as observed in our earlier cases of self‐assembly of peptide‐poly(methyl methacrylate) (peptide‐PMMA) or peptide‐poly(tert‐butyl methacrylate) (peptide‐P t BuA) conjugates in organic solvent . The appearance of such micelles in this case is attributed to the difference in polarities between peptide segment and PDMAEMA block.…”

“…Such deviation from linearity in both semilogarithmic and M n,SEC versus conversion (%) plots can be explained in the following way. We suggested that the concentration of initially used catalyst system (CuBr/HMTETA) decreased progressively during the course of polymerization due to the formation of copper complex with the added peptide‐initiator via amide groups, as reported by us and other groups …”

“…These primary micelles would not undergo secondary aggregation as there is no interaction among the PDMAEMA chains present in the corona of micelle. However, in our earlier cases of peptide‐PMMA and peptide‐P t BuA conjugates, the presence of secondary noncovalent interactions among the peptide segments of the corona of primary micelles resulted further aggregation among the primary micelles, which leads to the formation of composite micelle.…”

“…To prepare peptide‐initiator, the tripeptide, MeO‐Phe‐Leu‐Phe‐NH 2 was first synthesized using the similar procedure as described in our earlier report . The peptide‐initiator was then synthesized from MeO‐Phe‐Leu‐Phe‐NH 2 peptide via a standard solution‐phase coupling method using BIBB.…”

“…The peptide‐initiator was then synthesized from MeO‐Phe‐Leu‐Phe‐NH 2 peptide via a standard solution‐phase coupling method using BIBB. The synthesis protocol was also similar to our earlier report . Typically, 5 mL of DMF solution containing the peptide (2 g, 4.55 mmol) was cooled in an ice‐water bath followed by the addition of NEt 3 (635 μL, 4.55 mmol).…”