Thermosensitive micelles from PEGylated oligopeptides

New thermosensitive and micelle-forming diblock copolymers were synthesized by amide coupling of carboxylated methoxy-poly(ethylene glycols) with hydrophobic oligopeptides and characterized by means of 1H NMR spectroscopy, elemental analysis, and dynamic light scattering (DLS) measurements. Stable micelles were formed from copolymers composed of MPEG550 or MPEG750 as a hydrophilic segment and the hexapeptide, GlyPheLeuGlyPheLeuEt, as a hydrophobic segment. All the present diblock copolymers exhibited thermosensitive properties by showing a lower critical solution temperature (LCST) in water. The LCST of the copolymers composed of relatively shorter MPEG350 and GlyPheLeuAspEt2 was observed at much higher temperature (48 °C) compared with the LCST (29 °C) of the cyclotriphosphazene analogues bearing the same hydrophilic and hydrophobic segments as side groups. The remarkably lower LCST of the cyclotriphosphazene analogue is presumed to be due to the structural effect of the cis-nongeminal conformation of its three hydrophobic oligopeptides, but such a structural effect was found to diminish as the chain lengths of the hydrophilic and hydrophobic blocks of the copolymers increased.