Technische Universitat Munchen

Xl-protein Gmbh

Uli Binder

Arne Skerra

Martin Schlapschy

Stefan Achatz

The present invention relates to a nucleic acid molecule comprising a low repetitive nucleotide sequence encoding a proline/alanine-rich amino acid repeat sequence. The encoded polypeptide comprises a repetitive amino acid sequence that forms a random coil. The nucleic acid molecule comprising said low repetitive nucleotide sequences can further comprise a nucleotide sequence encoding a biologically or pharmacologically active protein. Further, the present invention provides for selection means and methods to identify said nucleic acid molecule comprising said low repetitive nucleotide sequence. The present invention also relates to a method for preparing said nucleic acid molecules. Also provided herein are methods for preparing the encoded polypeptide or drug conjugates with the encoded polypeptide using the herein provided nucleic acid molecules. The drug conjugate may comprise a biologically or pharmacologically active protein or a small molecule drug. Also provided herein are vectors and hosts comprising such nucleic acid molecules.

Nucleic acids encoding repetitive amino acid sequences rich in proline and alanine residues that have low repetitive nucleotide sequences

The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, in which the biosynthetic random coil polypeptide, the biosynthetic random coil polypeptide segment, or the biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein the amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. The at least about 50 proline (Pro) and alanine (Ala) amino acid residues may be (a) fconstituent(s) of a heterologous polypeptide or an heterologous polypeptide construct. Also uses and methods of use of these biosynthetic random coil polypeptides or polypeptide segments or conjugates are described.

Biosynthetic proline/alanine random coil polypeptides and their uses

The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, in which the biosynthetic random coil polypeptide, the biosynthetic random coil polypeptide segment, or the biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein the amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. The at least about 50 proline (Pro) and alanine (Ala) amino acid residues may be (a) constituent(s) of a heterologous polypeptide or an heterologous polypeptide construct. Also uses and methods of use of these biosynthetic random coil polypeptides or polypeptide segments or conjugates are described.

We discovered that a biosynthetic polypeptide, consisting of at least about 50 proline (Pro) and alanine (Ala) amino acid residues, forms a random coil, and increases the stability of other compounds to which it is conjugated, such as small molecules and polypeptides. We describe such biosynthetic polypeptides, constructs containing such polypeptides, ways of making them, and their use.

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Freising, Germany

Uli Binder