Poly(amino acid)-b-Poly(N,N-diethylacrylamide)-b-Poly(amino acid) Conjugates of Well-Defined Structure

Abstract

Carboxy-terminated oligomers of N,N-diethylacrylamide (DEAAm) with low polydispersity were synthesized by group-transfer polymerization. The oligomers were conjugated with the N terminus of epsilon-N-CBZ-protected poly(lysine) and s-CBZ-protected poly(L-cysteine). The resulting conjugates precipitated in a narrow region of lower critical solution temperatures (LCST) around 29 degrees C. The LCST of poly(lysine)-polyDEAAm-poly(lysine) conjugates was pH-independent and independent of the lengths of poly(lysine) segments. Water-soluble nonstoichiometric conjugate-DNA complexes precipitated above the conjugate's LCST. Covalent complexes of human albumin and poly(cysteine)-polyDEAAm-poly(cysteine) conjugates showed temperature-sensitive behaviour in aqueous solutions.

Associative diblock copolymers of poly(ethylene glycol) and coiled-coil peptides

“…Abbreviations 14p, (VSSLESK) 2 ; 21p, (VSSLESK) 3 ; 28p, (VSSLESK) 4 ; 35p, (VSSLESK) 5 ; 42p, (VSSLESK) 6 ; Boc, tert-butoxycarbonyl; CD, circular dichroism; DCM, dichloromethane; DIC, diisopropylcarbodiimide; DIEA, diisopropylethylamine; DMF, N,N-dimethylformamide; Fmoc, fluorenylmethyloxycarbonyl; FPLC, fast protein liquid chromatography; HOBt, 1-hydroxybenzotriazole; HPLC, high-pressure liquid chromatography; MALDI-TOF MS, matrix-assisted laser desorptionionization time-of-flight mass spectrometry; mPEG, amethoxy-poly(ethylene glycol); PBS, phosphate-buffered saline; PEG21, mPEG-21p; PEG28, mPEG-28p; PEG35, mPEG-35p; PEG42, mPEG-42p; PIP, piperidine; cPro, pseudoproline; PyBOP, benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate; RI, refractive index; SEC, size-exclusion chromatography; SPPS, solid-phase peptide synthesis; tBu, tert-butyl; TFA, trifluoroacetic acid; TFE, trifluoroethanol; TIS, triisopropylsilane.…”

“…(VSSLESK) 2 , (VSSLESK) 4 , (VSSLESK) 5 , (VSSLESK) 6 , mPEG-(VSSLESK) 4 , mPEG-(VSSLESK) 5 , and mPEG-(VSSLESK) 6 were prepared by the general method described above and characterized by MALDI-TOF MS, HPLC and FPLC. (Table 1, Figure 1).…”

“…The possibility to prepare such materials based on a combination of natural polymers (peptides and proteins) and synthetic polymers, considerably expands the design options. [5][6][7] The properties of such hybrid materials are controlled by the primary structure of the peptide part and by the character of the synthetic polymer. [8] Tailor-made block copolymers may self-assemble into novel supramolecular structures, which possess functional properties for drug delivery.…”

“…[12] Triblock BAB [4] or A 1 A 2 A 1 [6] copolymers have been designed to be sensitive to external stimuli (temperature and/or pH). Depending on the composition of the copolymers and the environmental conditions, these copolymers may form either micelles or assemble into hydrogels.…”

“…Depending on the composition of the copolymers and the environmental conditions, these copolymers may form either micelles or assemble into hydrogels. [6] Investigations on the design and properties of hybrid hydrogels have demonstrated that combining the exactly defined chemical structure of ''tailor-made'' polypeptides with readily available synthetic polymers may lead to the discovery of a completely new class of materials for various applications. For example, the incorporation of a peptide motif into hydrogels may impose the peptide's properties onto the whole system.…”