Lanthiopep B.v.

Applied Nanosystems B.v.

Morphosys Ag

Gert Nikolaas Moll

Rick Rink

Sieger Adriaan Nelemans

Louwe De Vries

Antonius Jacobus Marinus Roks

Anneke Kuipers

Arnold Jacob Driessen

Cornelis Johannes Leenhouts

Oscar Paul Kuipers

Rick Rinck

Marijke Haas

Leonardus Dorothea Kluskens

Arnold Jacob Mathieu Driessen

The invention relates to novel pharmaceutically-useful peptides, in particular cyclic peptides that are agonists of the AngII type 2 receptor (AT2 receptor). The invention further relates to the use of such peptides as medicaments, to pharmaceutical compositions containing them, and to their production.

Angiotensin type 2 (AT2) receptor agonists and uses thereof

Angiotensin Type 2 (AT2) receptor agonists and uses thereof

The invention relates to analogs of angiotensins, in particular to cyclised analogs having Ang(1-8) agonistic or antagonistic activity and to cyclised Ang(1-7) analogs with agonistic or antagonistic activity and displaying improved proteolytic resistance compared to their linear counterparts. Provided is a cyclic angiotensin peptide analog comprising a thioether-bridge linkage between the amino acids corresponding to positions Tyrand Proin naturally occurring Angiotensin. Also provided is the use of analogs in therapy, for example hypertension.

Cyclic angiotensin analogs

The invention relates to the production of heterologous polypeptides in a recombinant host cell. More specifically, it relates to the production and secretion of peptides, such as biologically active peptides, that are modified by one or more lantibiotic-synthesizing enzymes. Provided is a nucleic acid construct encoding a polypeptide comprising 1) a non-lantibiotic export signal that is recognized by a non-lantibiotic export system; 2) a lantibiotic leader peptide that is recognized by at least a lantibiotic dehydratase such as LanB and, C-terminally of said export signal and said leader peptide, 3) a peptide of interest containing one or more serine or threonine residue(s) which can be posttranslationally dehydrated by said dehydratase. Also provided is a method for producing a polypeptide in a host cell, comprising providing a host cell with a nucleic acid construct according to the invention and allowing expression and secretion of the encoded polypeptide by said host cell, wherein said host cell comprises at least a dehydratase capable of modifying said encoded polypeptide and a non-lantibiotic export system capable of secreting said modified polypeptide.

Methods for the production and secretion of modified peptides

The invention includes a method for harvesting a polypeptide produced by a host cell, wherein the polypeptide has not undergone intracellular posttranslational modification, such as dehydration of a serine or a threonine, and/or thioether bridge formation. The invention also includes a method for producing thioether-containing peptides and dehydroalanine/dehydrobutyrine-containing.peptides, wherein thioether rings may be formed extracellularly.

Export and modification of (poly)peptides in the lantibiotic way

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Groningen, Netherlands

Gert Nikolaas Moll