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 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 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.

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 a 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 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 novel, specific-binding therapeutic and/or diagnostic proteins directed against Hepcidin, which proteins preferably are muteins of a lipocalin protein. The invention also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, the invention also is directed to pharmaceutical and/or diagnostic compositions comprising such a lipocalin proteins, including uses of these proteins.

Abstract: A process for producing alanine, including culturing a cell under aerobic conditions in an aqueous phase in the presence of an inorganic nitrogen source, and then contacting the aqueous phase and the cell cultured in the aqueous phase with a hydrophobic organic phase. The cell is a prokaryotic or a lower eukaryotic cell and expresses a recombinant alanine dehydrogenase.

Abstract: The present disclosure relates to a collection of novel muteins derived from human ?1m (or a1m) polypeptide or a functional homolog 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 hydroxyindalpine derivatives of formula (I) as defined herein and pharmaceutical compositions comprising these compounds, as well as their medical use, particularly in the treatment or prevention of gastrointestinal diseases/disorders, such as constipation and functional dyspepsia.

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 inventors have solved the crystal structure of an Escherichia coli bacterial lipocalin polypeptide, which depicts a monomeric protein. Previous crystal structures have been reported, but these appear to he inaccurate, as they predicted, e.g., a dimeric protein. The crystal structure of a bacterial lipocalin provided by the present invention leads to numerous uses. For example, the present invention provides for the design, construction and use of recombinant libraries of diversified bacterial lipocalins resulting from a bacterial lipocalin polypeptide “backbone”.

Abstract: A method including the steps a) providing a primary alcohol of the formula HO—(CH2)x—R1, where R1 is —OH, —SH, —NH2 or —COOR2; x is at least 3; and R2 is H, alkyl or aryl, b) oxidizing the primary alcohol by contacting it with an NAD(P)+-dependent alcohol dehydrogenase, and c) contacting the oxidation product of step a) with a transaminase, where the NAD(P)+-alcohol dehydrogenase and/or the transaminase is a recombinant or isolated enzyme. A whole cell catalyst for carrying out the method. The use of such a whole cell catalyst for oxidizing a primary alcohol.

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 invention relates to the production of novel proteins exhibiting bonding activity for certain ligands, the so-called anticalins. To this end, the structure of peptides of the lipocalin family is modified by amino acid replacement in their natural ligand binding pocket using generic engineering methods. A like immunoglobulin, the anticalin thus obtained can be used to identify or bond molecular structures.

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 a 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 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) constituents) 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.

Abstract: Increased in vivo and/or in vitro stability is imparted to a biologically active protein by fusing to an amino acid sequence consisting of at least about 100 amino acid residues, which consist essentially of Alanine, Serine and Proline, which form a random coil conformation. Specific examples are described. Also described are related nucleic acids, vectors and cells encoding such amino acids; compositions of biologically active proteins fused to a random coil domain, and methods of making and using the compounds and compositions of the invention.

Abstract: The present invention relates to hydroxyindalpine derivatives of formula (I) as defined herein and pharmaceutical compositions comprising these compounds, as well as their medical use, particularly in the treatment or prevention of gastrointestinal diseases/disorders, such as constipation and functional dyspepsia.

Abstract: 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.

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 a 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.