title: Calcium binding peptide motifs from calmodulin confer divalent ion selectivity to elastin-like polypeptides.
abstract: Calcium-sensitive elastin-like polypeptides (CELPs) were synthesized by periodically interspersing a calcium-binding peptide sequence from calmodulin within an elastin-like polypeptide (ELP) with the goal of creating thermal and calcium responsive peptide polymers. The CELPs exhibit high sensitivity to calcium compared to monovalent cations but do not exhibit the exquisite selectivity for calcium over other divalent cations, such as magnesium, that is displayed by calmodulin. The CELPs were further used as a building block for the synthesis of calcium-sensitive nanoparticles by fusing a hydrophilic, noncalcium-sensitive ELP block with a CELP block that becomes more hydrophobic upon calcium binding. We show that addition of calcium at concentrations between 50 and 500 mM imparts sufficient amphiphilicity to the diblock polypeptide between 33 and 46 °C to trigger its self-assembly into monodisperse spherical micelles with a hydrodynamic radius of ∼50 nm.
authors.affiliation: Department of Biomedical Engineering, Campus Box 90281, Duke University, Durham, North Carolina 27708, United States.
authors.forename: Wafa
authors.initials: W
authors.lastname: Hassouneh
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Nunalee
authors.forename: M Coleman
authors.initials: MC
authors.lastname: Shelton
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D002413:Cations, Divalent; D004549:Elastin / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D052139:Intracellular Calcium-Sensing Proteins / Q000138:chemical synthesis*; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis; D013501:Surface-Active Agents
chemical_list: D002147:Calmodulin; D002413:Cations, Divalent; D052139:Intracellular Calcium-Sensing Proteins; D010455:Peptides; D011108:Polymers; D013501:Surface-Active Agents; D004549:Elastin; D002118:Calcium