Artificial Protein Block Polymer Libraries Bearing Two SADs: Effects of Elastin Domain Repeats

Abstract

We have generated protein block polymer E(n)C and CE(n) libraries composed of two different self-assembling domains (SADs) derived from elastin (E) and the cartilage oligomeric matrix protein coiled-coil (C). As the E domain is shortened, the polymers exhibit an increase in inverse transition temperature (T(t)); however, the range of temperature change differs dramatically between the E(n)C and CE(n) library. Whereas all polymers assemble into nanoparticles, the bulk mechanical properties of the E(n)C are very different from CE(n). The E(n)C members demonstrate viscolelastic behavior under ambient conditions and assemble into elastic soft gels above their T(t) values. By contrast, the CE(n) members are predominantly viscous at all temperatures. All library members demonstrate binding to curcumin. The differential thermoresponsive behaviors of the E(n)C and CE(n) libraries in addition to their small molecule recognition abilities make them suitable for potential use in tissue engineering and drug delivery.

Noncovalent Modulation of the Inverse Temperature Transition and Self-Assembly of Elastin-b-Collagen-like Peptide Bioconjugates

“…4f,25 There have been very limited reports of thermoresponsive nanostructures that can be assembled from short synthetic ELPs. 6,26 Our studies illustrate that this barrier can be overcome by simply anchoring three ELP chains to a collagen triple helix. This not only exploits the reversibility of triple helix formation to modulate the transition temperature of the molecules over a wide range, but should also permit manipulation of the size of the vesicles.…”

Protein based therapeutic delivery agents: Contemporary developments and challenges

“…More recently the Montclare group has focused on the evolution of both coiled-coil- and ELP-based delivery strategies by interrogating a hybrid construct approach [91, 150]. The fusion with ELP repeats allow a COMPcc-based diblock and triblock copolymer to be thermoresponsive with transition temperatures ranging from 27.0 °C to 59.0 °C and particle diameters between 20 and 30 nm [91, 150].…”

“…The fusion with ELP repeats allow a COMPcc-based diblock and triblock copolymer to be thermoresponsive with transition temperatures ranging from 27.0 °C to 59.0 °C and particle diameters between 20 and 30 nm [91, 150]. These properties allow these block copolymers to be potentially amenable to hyperthermia applications and leverage the EPR effect due to the proximity of the transition temperature to physiologic conditions and the < 200 nm particle size [27].…”

“…These properties allow these block copolymers to be potentially amenable to hyperthermia applications and leverage the EPR effect due to the proximity of the transition temperature to physiologic conditions and the < 200 nm particle size [27]. Interestingly, the exchange of the orientation between COMPcc and ELP domain created different mechanical behaviors [91, 150]. The library of COMPcc leading at the N-terminus in the diblock polymers exhibited viscous character at room temperature, which was applicable for drug delivery and indeed examined by the binding with CCM [91].…”

Polymerization of Peptide Polymers for Biomaterial Applications

“…Polypeptides such as collagen, elastin, and silk, are currently being sought as nextgeneration biomaterials (Table 2). [23][24][25][26][27][28] Collagen, a major constituent of bone, cartilage, tendon, skin and muscle, are the most abundant proteins in the human body. [29] Several different types of collagen have been identified; these proteins are distinguished by their triple-helical structure.…”