Abstract: The present invention relates to a novel library for the generation of muteins and to novel muteins derived from human lipocalin 2 (Lcn2, hNGAL) and related proteins that bind a given target with detectable affinity. The invention also relates to corresponding nucleic acid molecules encoding such a mutein and to a method for their generation. The invention further relates to a method for producing such a mutein. For example, such muteins may serve to bind and deplete pathological forms of natural biomolecules such as the amyloid beta peptide in Alzheimer's disease or may target the fibronectin extra-domain B, which is associated with tumor neovasculature.

Abstract: The present invention relates to a nucleic acid molecule encoding a fusion protein comprising (i) a secretory signal peptide; (ii) a lipocalin-derived binding protein specifically binding to an exogenous ligand; and (iii) a glycosylphosphatidylinositol (GPI) anchored and/or transmembrane domain.

Abstract: The present invention relates to a prostate-specific membrane antigen (PSMA)-specific binding protein, wherein the PSMA-specific binding protein is a lipocalin 2 (Lcn2)-derived binding protein and binds to PSMA with a KD of 10 nM or lower. The present invention also relates to a nucleic acid molecule encoding the PSMA-specific binding protein of the invention, a vector comprising said nucleic acid molecule of the invention and a host cell transformed with the vector. Furthermore, the invention relates to a method of producing the PSMA-specific binding protein of the invention, the method comprising culturing the host cell of the invention under suitable conditions and isolating the PSMA-specific binding protein produced. The present invention further relates to a protein conjugate comprising the PSMA-specific binding protein of the invention, or the PSMA-specific binding protein produced by the method of the invention.

Abstract: 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.

Abstract: The present invention relates to a cluster of differentiation 98 heavy chain (CD98hc)-specific binding protein, wherein the CD98hc-specific binding protein is a lipocalin 2 (Lcn2)-derived binding protein and binds to CD98hc with a KD of 200 nM or lower.

Abstract: There is provided a microbial cell expressing a mutant AlkB enzyme, the mutant AlkB enzyme comprising at least one point mutation in the wild type sequence of AlkB, wherein the point mutation is at amino acid position V129 and/or T136 of the wild type AlkB enzyme. There is also provided a method for producing omega-hydroxy carboxylic acid and/or ester thereof using this cell.

Abstract: The present invention relates to a light-switchable polypeptide. In particular, the present invention relates to a polypeptide comprising a light-responsive element, wherein the configuration (i.e. the configurational state) of the light-responsive element can be switched between a trans and cis isomer by irradiating the polypeptide with (a) particular wavelength(s) of light, and wherein the switch of said configuration alters the conformation and binding activity of said polypeptide to a ligand (e.g. molecule of interest). Also, the present invention comprises using said light-switchable polypeptide for isolating and/or purifying a molecule of interest. The present invention further provides an affinity matrix, an affinity chromatography column, and an affinity chromatography apparatus comprising the light-switchable polypeptide of the invention.

Abstract: A method is useful for the biocatalytic synthesis of proteinogenic L-amino acids, such as L-alanine, L-valine, L-methionine, L-leucine, L-isoleucine or L-phenylalanine from a respective aldehyde and carbon dioxide. In particular, the method is useful for the biocatalytic synthesis of L-methionine from 3-methylthio-propanal (“methional”) and carbon dioxide.

Abstract: 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.

Abstract: The invention relates to an enzymatic method for producing 2-hydroxy-4-methylmercaptobutanoic acid from 3-methylthio-propanal (3-methylmercaptopropanal (MMP) or “methional”) and carbon dioxide.

Abstract: The present invention relates to a novel library for the generation of muteins and to novel muteins derived from human lipocalin 2 (Lcn2, hNGAL) and related proteins that bind a given target with detectable affinity. The invention also relates to corresponding nucleic acid molecules encoding such a mutein and to a method for their generation. The invention further relates to a method for producing such a mutein. For example, such muteins may serve to bind and deplete pathological forms of natural biomolecules such as the amyloid beta peptide in Alzheimer's disease or may target the fibronectin extra-domain B, which is associated with tumor neovasculature.

Abstract: The present disclosure relates to a collection of novel muteins derived from human ?1m (or a1m) polypeptide or a functional homologue thereof. The disclosure further refers to a ?1m mutein capable of specifically binding to one or more targets other than a target to which wild-type ?1m binds. The disclosure also relates to a method for producing such collection of muteins and a method for isolating a mutein capable of binding one or more such non-natural targets of wild-type ?1m polypeptide. These aspects are made possible due to, e.g, the structural elucidation of ?1m disclosed herein by the present inventors, an appreciation of ligand-binding sights thereof and, hence, an understanding of which amino acid positions are most suitable for mutagenesis for re-engineering specificity and affinity for any given target while maintaining the secondary and/or tertiary structure of a1m.

Abstract: The present invention relates to a novel library for the generation of muteins and to novel muteins derived from human lipocalin 2 (Lcn2, hNGAL) and related proteins that bind a given target with detectable affinity. The invention also relates to corresponding nucleic acid molecules encoding such a mutein and to a method for their generation. The invention further relates to a method for producing such a mutein. For example, such muteins may serve to bind and deplete pathological forms of natural biomolecules such as the amyloid beta peptide in Alzheimer's disease or may target the fibronectin extra-domain B, which is associated with tumor neovasculature.

Abstract: The present invention relates to a prostate-specific membrane antigen (PSMA)-specific binding protein, wherein the PSMA-specific binding protein is a lipocalin 2 (Lcn2)-derived binding protein and binds to PSMA with a KD of 10 nM or lower. The present invention also relates to a nucleic acid molecule encoding the PSMA-specific binding protein of the invention, a vector comprising said nucleic acid molecule of the invention and a host cell transformed with the vector. Furthermore, the invention relates to a method of producing the PSMA-specific binding protein of the invention, the method comprising culturing the host cell of the invention under suitable conditions and isolating the PSMA-specific binding protein produced. The present invention further relates to a protein conjugate comprising the PSMA-specific binding protein of the invention, or the PSMA-specific binding protein produced by the method of the invention.

Abstract: A method is useful for the biocatalytic synthesis of proteinogenic L-amino acids, such as L-alanine, L-valine. L-methionine. L-leucine, L-isoleucine or L-phenylalanine from a respective aldehyde and carbon dioxide. In particular, the method is useful for the biocatalytic synthesis of L-methionine from 3-methylthio-propanal (“methional”) and carbon dioxide.

Abstract: The present invention relates to a prostate-specific membrane antigen (PSMA)-specific binding protein, wherein the PSMA-specific binding protein is a lipocalin 2 (Lcn2)-derived binding protein and binds to PSMA with a KD of 10 nM or lower. The present invention also relates to a nucleic acid molecule encoding the PSMA-specific binding protein of the invention, a vector comprising said nucleic acid molecule of the invention and a host cell transformed with the vector. Furthermore, the invention relates to a method of producing the PSMA-specific binding protein of the invention, the method comprising culturing the host cell of the invention under suitable conditions and isolating the PSMA-specific binding protein produced. The present invention further relates to a protein conjugate comprising the PSMA-specific binding protein of the invention, or the PSMA-specific binding protein produced by the method of the invention.

Abstract: There is provided a microbial cell expressing a mutant AlkB enzyme, the mutant AlkB enzyme comprising at least one point mutation in the wild type sequence of AlkB, wherein the point mutation is at amino acid position V129 and/or T136 of the wild type AlkB enzyme. There is also provided a method for producing omega-hydroxy carboxylic acid and/or ester thereof using this cell.

Abstract: The present invention relates to novel muteins derived from human tear lipocalin. The invention also refers to a corresponding nucleic acid molecule encoding such mutein and to a method for its generation. The invention further refers to a method for producing such a mutein. Finally, the invention is directed to a pharmaceutical composition comprising such a lipocalin mutein as well as to various uses of the mutein.

Abstract: 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.

Abstract: The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, wherein said biosynthetic random coil polypeptide, said biosynthetic random coil polypeptide segment or said biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein said amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. Said 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 said conjugates are described.