The present invention relates to purified peptidomimetic macrocycles. The invention additionally provides methods of preparing and using such macrocycles, for example in therapeutic applications.

The present invention relates to purified peptidomimetic macrocycles. The invention additionally provides methods of preparing and using such macrocycles, for example in therapeutic applications.

The present invention relates to a composition consisting of or containing peptides selected from the group consisting of or containing RD2, D3, homologs having at least 50% identity and derivatives of RD2 or D3 and also polymers containing or consisting of RD2/D3 homologs having at least 50% identity and derivatives of RD2 and under D3 for use as an analgesic, for use in pain therapy, for use in the treatment of chronic and/or neuropathic pain and/or for inhibiting N-type neuronal calcium channels (NCCs).

The present invention relates to a composition consisting of or containing peptides selected from the group consisting of or containing RD2, D3, homologs having at least 50% identity and derivatives of RD2 or D3 and also polymers containing or consisting of RD2/D3 homologs having at least 50% identity and derivatives of RD2 and under D3 for use as an analgesic, for use in pain therapy, for use in the treatment of chronic and/or neuropathic pain and/or for inhibiting N-type neuronal calcium channels (NCCs).

The present invention relates to peptides with alternating stereochemistry. In particular, the invention relates to peptides comprising alternating stereochemistry of (LDLD) in the first four amino acid residues. The invention further contemplates the use of peptides with alternating stereochemistry in treating pain.

A process for the production of a glycoconjugate by N-glycosylation of a protein or peptide comprising the sequence D/E-X-N-X-S/T (SEQ ID NO:1), wherein each X is the same or different and is any natural amino acid other than proline, wherein the process comprises reacting the protein or peptide with a polyisoprenyl pyrophosphate of formula (I), or a salt thereof, in the presence of PglB:

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to produce the glycoconjugate comprising the protein or peptide having a saccharide [S1] linked to the asparagine in the sequence D/E-X-N-X-S/T (SEQ ID NO:1). Polyisoprenylpyrophosphates used as substrates in the biocatalytic process are also provided, as well as certain glycoconjugates.

A process for the production of a glycoconjugate by N-glycosylation of a protein or peptide comprising the sequence D/E-X-N-X-S/T (SEQ ID NO:1), wherein each X is the same or different and is any natural amino acid other than proline, wherein the process comprises reacting the protein or peptide with a polyisoprenyl pyrophosphate of formula (I), or a salt thereof, in the presence of PglB:

##STR00001##

to produce the glycoconjugate comprising the protein or peptide having a saccharide [S1] linked to the asparagine in the sequence D/E-X-N-X-S/T (SEQ ID NO:1). Polyisoprenylpyrophosphates used as substrates in the biocatalytic process are also provided, as well as certain glycoconjugates.

Disclosed are methods, systems, components, and compositions for cell-free synthesis of glycosylated proteins. The glycosylated proteins may be utilized in vaccines, including anti-bacterial vaccines. The glycosylated proteins may include a bacterial polysaccharide conjugated to a carrier, which may be utilized to generate an immune response in an immunized host against the polysaccharide conjugated to the carrier. The glycosylated proteins may be synthesized in cell-free glycoprotein synthesis (CFGpS) systems using prokaryote cell lysates that are enriched in components for glycoprotein synthesis such as oligosaccharyltransferases (OSTs) and lipid-linked oligosaccharides (LLOs) including OSTs and LLOs associated with synthesis of bacterial O antigens.

The disclosure discloses an Aspergillus niger engineered strain for reducing byproduct succinic acid in a fermentation process of L-malic acid. The Aspergillus niger engineered strain is an Aspergillus niger engineered strain in which fumaric acid reductase frdA and fumaric acid reductase flavoprotein subunit frdB are simultaneously knocked out. The disclosure provides an frdA and frdB gene double-knockout Aspergillus niger strain, and a method for greatly reducing byproduct succinic acid in a fermentation process of L-malic acid. By the disclosure, the byproduct succinic acid accumulated in a production process of malic acid through fermentation of Aspergillus niger is significantly reduced, a cost in a downstream separation and purification process of malic acid is decreased, and good strains are provided for producing malic acid via industrial fermentation.

The present disclosure described herein provides compositions with a membrane-penetrating properties and methods for allowing translocation across a membrane without disruption.