Library of random copolypeptides by solid phase synthesis.

Random copolypeptides are promising and versatile bioinspired macromolecules of minimal complexity for studying their interactions with both living and synthetic matter. They provide the opportunity to investigate the role of, for example, total net charge and hydrophobicity through simply changing the monomer composition, without considering the effect of specific sequences or secondary structure. However, synthesizing large libraries of these polymers so far was prohibited by the time-consuming preparation methods available (ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides and enzymatic polymerization of amino acids). Here we report the automated solid phase synthesis (SPS) of a complete library of polypeptides containing Glu, Lys, and Ala monomers with excellent control over the degree of polymerization and composition and with polydispersity indices (PDIs) between 1.01 and 1.001, which is impossible to achieve by other methods. This method provides access to a library of polymers with a precisely defined total charge that can range from approximately -15 to +15 per chain and with a disordered conformation almost completely devoid of any secondary structure. In solution the polymers are largely present as unimers, with only the most hydrophobic polypeptides showing slight signs of aggregation. Our new approach provides convenient access to libraries of this versatile class of polymers with tunable composition, which can be used in a wide variety of physicochemical studies as a tool that allows systematic variation of charge and hydrophobicity, without the interference of secondary structure or aggregation on their performance.

Ion-association complexes unite classical and non-classical theories for the biomimetic nucleation of calcium phosphate.

Despite its importance in many industrial, geological and biological processes, the mechanism of crystallization from supersaturated solutions remains a matter of debate. Recent discoveries show that in many solution systems nanometre-sized structural units are already present before nucleation. Still little is known about the structure and role of these so-called pre-nucleation clusters. Here we present a combination of in situ investigations, which show that for the crystallization of calcium phosphate these nanometre-sized units are in fact calcium triphosphate complexes. Under conditions in which apatite forms from an amorphous calcium phosphate precursor, these complexes aggregate and take up an extra calcium ion to form amorphous calcium phosphate, which is a fractal of Ca(2)(HPO(4))(3)(2-) clusters. The calcium triphosphate complex also forms the basis of the crystal structure of octacalcium phosphate and apatite. Finally, we demonstrate how the existence of these complexes lowers the energy barrier to nucleation and unites classical and non-classical nucleation theories.