The present invention relates to a liquid (or solution)-phase manufacturing process for preparing the decapeptide Degarelix, its protected precursor, and other useful intermediates. The invention further relates to polypeptides useful in the solution-phase manufacturing process and to the purification of Degarelix itself. Degarelix can be obtained by subjecting a Degarelix precursor according to formula II: (P.sub.1)AA.sub.1-AA.sub.2-AA.sub.3-AA.sub.4(P.sub.4)-AA.sub.5-AA.sub.6(P.sub.6)-AA.sub.7-AA.sub.8(P.sub.8)-AA.sub.9-AA.sub.10-NH.sub.2 (II) or a salt or solvate thereof, to a treatment with a cleaving agent in an organic solvent, wherein P.sub.1 is an amino protecting groups; preferably acetyl; P.sub.4 is hydrogen or a hydroxyl protecting group, preferably a hydroxyl protecting group; P.sub.6 is hydrogen or an amino protecting groups; preferably an amino protecting groups; and P.sub.8 is an amino protecting group.

The present application relates to an improved process for the formation of disulfide bonds in linaclotide. The present application also relates to an improved process for the purification of linaclotide.

The present application relates to an improved process for the formation of disulfide bonds in linaclotide. The present application also relates to an improved process for the purification of linaclotide.

The present invention provides for methods and compositions for treating or preventing arthritis and joint injury.

A process for preparing amides by reacting a primary amine and a primary alcohol in the presence of a Ruthenium complex to generate the amide and molecular hydrogen. Primary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen (the only byproduct) in high yields and high turnover numbers. Also disclosed are processes for hydrogenation of amides to alcohols and amines; hydrogenation of organic carbonates to alcohols; hydrogenation of carbamates or urea derivatives to alcohols and amines; amidation of esters; acylation of alcohols using esters; coupling of alcohols with water and a base to form carboxylic acids; dehydrogenation of beta-amino alcohols to form pyrazines and cyclic dipeptides; and dehydrogenation of secondary alcohols to ketones. These reactions are catalyzed by a Ruthenium complex which is based on a dearomatized PNN-type ligand of formula A1 or precursors thereof of formulae A2 or A3.

The invention provides a method for producing a peptide by (1) removing the N-terminal protective group of an amino acid or peptide compound of formula (I):

##STR00001##

wherein Y represents a residue of an N-protected amino acid or an N-protected peptide, and each of R.sup.1, R.sup.2, and R.sup.3 independently represents an aliphatic hydrocarbon group which may have a substituent or an aromatic hydrocarbon group which may have a substituent, wherein the total number of carbon atoms in the R.sup.1R.sup.2R.sup.3Si group is 18 to 80, and the R.sup.1R.sup.2R.sup.3SiCH.sub.2CH.sub.2 group is bonded to the C-terminus of the amino acid or peptide residue in Y; and (2) causing condensation of an N-protected amino acid or an N-protected peptide and the N-terminus of the C-protected amino acid or C-protected peptide obtained in the step (1).

A semi-recombinant method for the production of GLP-1 analogues and derivatives with non-proteogenic amino acids in the N-terminal part combining the use of recombinant expression techniques and chemical peptide synthesis.

A semi-recombinant method for the production of GLP-1 analogues and derivatives with non-proteogenic amino acids in the N-terminal part combining the use of recombinant expression techniques and chemical peptide synthesis.

The present disclosure provides a method of solid-phase peptide synthesis from the N terminus to C terminus without detectable epimerization of the C-terminal amino acid. The method includes using derivatized amino acids comprising a diamino-aryl group.

A deep eutectic solvent consisting of (2-hydroxyethyl) trimethyl ammonium chloride and dithiothreitol in a molar ratio of from 1:2 to 1:3 and from 0% to 10% co-solvent, and methods of enzymatic production of polypeptides using the deep eutectic solvent.