Polypeptide dopé au métabolisme en 2025
Le sous-traitant de l'industrie pharmaceutique Polypeptide a profité l'an dernier de l'essor des thérapies métaboliques. Son chiffre d'affaires s'est enrobé de plus de 15% pour avoisiner les 389 millions d'euros, selon un relevé préliminaire publié lundi. #Polypeptide #news
Polypeptide steigert Umsatz 2025 deutlich und verbessert Marge klar
Der Wirkstoffhersteller Polypeptide hat das Geschäftsjahr 2025 mit einem kräftigen Umsatzplus und einer markanten Verbesserung der Profitabilität abgeschlossen. Treiber des Wachstums waren vor allem Wirkstoffe für Stoffwechselerkrankungen, darunter Anwendungen im stark wachsenden GLP-1-Bereich. #Polypeptide #news
Polypeptide und Lupin Manufacturing schliessen Allianz für Peptid-Lieferketten
Polypeptide und der indische Auftragsfertiger Lupin Manufacturing Solutions schliessen sich zu einer strategischen Allianz zusammen. Ziel ist es, die Versorgungssicherheit bei Peptiden für Stoffwechseltherapien zu stärken. #Polypeptide #news
Polypeptide hebt Prognose nach erfolgreichem ersten Semester an
Polypeptide schaut auf ein sehr erfolgreiches erstes Halbjahr 2025 zurück, unter dem Strich ist aber erneut ein Verlust angefallen. Für das Gesamtjahr passt der Auftragsentwickler und -hersteller von Peptiden seine Wachstumsprognosen nun leicht nach oben an. #Polypeptide #news
Malgré des revenus en hausse, Polypeptide a creusé sa perte après six mois
Tirant notamment profit du bon démarrage de sa nouvelle ligne de production sur le site belge de Braine-l'Alleud, Polypeptide a fortement accru ses ventes au premier semestre. #Polypeptide #news
PolyPeptide weitet Kreditrahmen aus und bekommt Unterstützung von Hauptaktionär
Der Pharmaauftragsfertiger PolyPeptide verschafft sich mehr finanzielle Flexibilität. Dazu wird der bestehende Kreditrahmen ausgeweitet und auch der Hauptaktionär Draupnir Holding verstärkt seine Unterstützung. #Polypeptide #news
Polypeptide baut Produktionskapazitäten in Malmö massiv aus
Der Auftragsfertiger Polypeptide nimmt rund 100 Millionen Euro in die Hand, um seine Produktionskapazitäten am Standort Malmö zu verdoppeln. Die Kapazitäten werden benötigt, um früher kommunizierte Grossaufträge erfüllen zu können. #Polypeptide #news
Polypeptide investit 100 millions d'euros dans son site suédois de Malmö
Le sous-traitant pharmaceutique d'origine suédoise Polypeptide entend doubler à terme les capacités de synthèse de son site de Malmö et annonce conséquemment un investissemement de 100 millions d'euros. L'opération doit permettre d'honorer un contrat d'approvisionnement déjà conclu et implique la création d'une centaine de nouveaux emplois. #Polypeptide #news
Fort d'un solide premier semestre, Polypeptide revoit ses objectifs à la hausse
Le sous-traitant pharmaceutique Polypeptide a vu ses recettes et sa rentabilité augmenter au premier semestre 2024. Optimiste, le groupe zougois a revu ses prévisions à la hausse pour l'ensemble de l'année. A moyen terme, il espère même doubler ses ventes. #Polypeptide #news
[#TRADESHOW] 2024 China International #Fertilizer #Show showcases #polypeptide #fertilizers, #chelate fertilizers, #water #soluble fertilizers, #microbial fertilizers and more. 13.-15. March, 2024. National #Exhibition and #Convention Center (NECC), #Shanghai, #China. https://cnbusinessforum.com/event/2024-china-international-fertilizer-show/
Polypeptide s'assure une ligne de crédit de plus de 100 millions
Le sous-traitant de l'industrie pharmaceutique Polypeptide s'est félicité lundi de la signature d'une facilité de crédit renouvelable de 111 millions d'euros sur trois ans auprès de Credit Suisse (CS), Danske Bank et la Banque cantonale de Zurich (ZKB). #Polypeptide #news
Polypeptide sichert sich revolvierende Kreditfazilität
Der Pharmazulieferer Polypeptide hat sich frische Mittel gesichert. Die bereits kommunizierten Finanzierungsverhandlungen hat das Unternehmen somit abgeschlossen. #Polypeptide #news
Polypeptide mit hohem Verlust im ersten Semester - Neuer Finanzchef
Der Pharmazulieferer Polypeptide hat ein schwaches erstes Semester hinter sich. Mit den endgültigen Halbjahreszahlen bestätigt der Auftragshersteller von Peptid-Wirkstoffen seine frühere Prognose, dass im Gesamtjahr 2023 wegen der schnellen Expansion des Geschäftes ein Verlust anfallen werde. #Polypeptide #news
#microRNAs slow translating #ribosomes to prevent protein #misfolding in eukaryotes
Hiroaki Sako, Tadashi Yamamoto and colleagues
The unusual presence of #miRNAs targeting protein-coding sequences is shown to influence ribosome speed, thereby allowing time for accurate #polypeptide folding during protein translation.
https://www.embopress.org/doi/full/10.15252/embj.2022112469
Polypeptide prévoit de basculer dans le rouge en 2023
Polypeptide souffre d'une hausse de sa base des coûts et d'une série d'effets uniques qui vont plomber sa rentabilité. Le fournisseur de peptides à l'industrie pharmaceutique table sur une perte nette au premier semestre et pour l'exercice 2023 dans son ensemble. #Polypeptide #news
Polypeptide spricht erneute Gewinnwarnung aus
Der Pharmazulieferer Polypeptide spricht seine dritte Gewinnwarnung in den letzten zwölf Monaten aus. Der Auftragshersteller von Peptid-Wirkstoffen rechnet sowohl im ersten Semester, also auch im gesamten Jahr 2023 mit einem Verlust. Das laufende Geschäftsjahr wird nun als "Übergangsjahr" angesehen. #Polypeptide #news
Dear Professor Scientists,
Good morning, I'm Grace, we learned about you by looking up information about the polypeptide on the Internet,
@RonBeavis what is the need for a new descriptor of a #polypeptide?
ATP-Driven Molecular Chaperone Machines
#Molecular #chaperones are proteins that help maintain the balance of proteins in the #cell, which is essential for the cell to stay alive. Chaperones are always present in the cell, but they can also be activated in response to #stress. They interact with proteins that are not folded correctly, preventing them from clumping together and helping them to fold correctly. Chaperones don't usually interact with proteins that are already folded correctly. They use #energy from #ATP binding and/or hydrolysis to help with #folding and unfolding proteins. Because chaperones are involved in keeping protein balance, they are linked to diseases caused by #protein misfolding, such as #neurodegeneration and #cancer. Therefore, understanding how chaperones work is important for understanding and treating these diseases.
The Hsp70 system is a group of proteins that are found in #bacteria, #eukaryotic cells, and some #archaea. They are responsible for binding to unfolded or partially unfolded proteins to prevent them from aggregating and to help them fold correctly. Hsp70 proteins are made up of two parts: a 44 kDa N-terminal ATPase domain and a 28 kDa substrate binding domain with a C-terminal lid subdomain. The #ATPase domain helps the protein bind and release substrates, while the substrate-binding domain binds to extended #polypeptide chains. Hsp40 proteins, which are also known as J-domain proteins, act as co-chaperones to Hsp70 and help recruit substrates and stimulate the ATPase activity of Hsp70. Hsp40s can also direct Hsp70 to specialized functions and sub-cellular regions.
Hsp90 is a type of molecular chaperone that helps proteins fold correctly. It is made up of three conserved domains: the ATP binding N-terminal domain, the middle domain, and the C-terminal dimerization domain. Hsp90 works by binding to proteins that need to be folded correctly and preventing them from aggregating in an ATP-dependent manner. It also interacts with other proteins, called co-chaperones, which help regulate its ATPase cycle and determine which proteins it binds to. Hsp90 can also act as a buffer for genetic variation by rescuing mutated proteins with altered properties.
The different functions of the Hsp100/Clp proteins.
These proteins contain one or two conserved ATPases Associated with various cellular Activities (AAA1) domains and can act as #unfoldases or #disaggregases. Unfoldases help to unfold proteins and deliver them to a ring #protease, while disaggregases have the unique ability to recover proteins from both amorphous and #amyloid aggregates. The main difference between the two is the presence of a coiled-coil insertion in the first AAA1 domain in the disaggregases. The Hsp100 proteins usually form hexamers which hydrolyze ATP in either a sequential/random or a concerted manner. #Crystal structures have been determined of monomeric forms of several Hsp100 proteins, and of the hexamer forms of HslU, ClpX, and ClpC unfoldases. Hexameric forms of various Hsp100’s have been observed at intermediate resolutions by cryo-EM. These structures suggest a typical AAA1 packing arrangement for the unfoldases and an expanded conformation for the Hsp104 disaggregase. The central channels of the Hsp100s are lined by tyrosine residues, located on mobile loops, which bind substrates non-specifically. It is thought that rotations of the AAA1 domains provide the force to unfold the bound substrate and pull it through the channel. Disaggregation and unfolding functions are coupled and regulated via an interaction between the Hsp70 nucleotide-binding domain and the coiled-coil insertion. Recent biochemical and structural data suggest that it is docked on the outside surface of the AAA1 ring. Hsp100/Clp proteins are proteins that have one or two conserved ATPases Associated with various cellular Activities (AAA1) domains. These proteins can act in two different ways: as unfoldases or disaggregases. Unfoldases help to unfold proteins and deliver them to a ring protease, while disaggregases have the ability to recover proteins from both amorphous and amyloid aggregates. The main difference between the two is the presence of a coiled-coil insertion in the first AAA1 domain in the disaggregases. The Hsp100 proteins usually form hexamers which hydrolyze ATP in either a sequential/random or a concerted manner. Structures of these proteins have been determined, which suggest a typical AAA1 packing arrangement for the unfoldases and an expanded conformation for the Hsp104 disaggregase. The central channels of the Hsp100s are lined by tyrosine residues, which bind substrates non-specifically. It is thought that rotations of the AAA1 domains provide the force to unfold the bound substrate and pull it through the channel. Disaggregation and unfolding functions are coupled and regulated via an interaction between the Hsp70 nucleotide-binding domain and the coiled-coil insertion, which is docked on the outside surface of the AAA1 ring.
GroEL is a molecular chaperone machine that binds to proteins to prevent them from aggregating. It is estimated that GroEL binds to around 10% of the proteins in E. coli. The binding site is hydrophobic in character and contains essential hydrophobic residues that line the cavity-facing surface of the apical domain. If one of these residues is changed from hydrophobic to hydrophilic, the binding is abolished. Studies have shown that multiple binding sites act together as a continuous hydrophobic binding surface. It has also been shown that proteins stably bound to #GroEL are unstructured and that binding of non-native proteins to GroEL can be associated with unfolding. X-ray crystallographic studies have revealed structures of extended or helical peptides bound in the groove formed by helices H and I via hydrophobic interactions. Cryo-EM has also been used to probe the structure of non-native proteins bound to GroEL, which showed that the substrates were bound to helices H and I, with substrate density protruding from the GroEL ring. There is an upper limit, around 60 kDa, to the size of substrate that can fit inside the folding chamber. In summary, GroEL is a molecular chaperone machine that binds to proteins to prevent them from aggregating. It has a hydrophobic binding site that contains essential hydrophobic residues. Studies have shown that multiple #binding sites act together as a continuous hydrophobic binding surface and that proteins stably bound to GroEL are unstructured. X-ray crystallographic and cryo-EM studies have revealed structures of extended or helical peptides bound in the groove formed by helices H and I via hydrophobic interactions. The upper limit to the size of substrate that can fit inside the folding chamber is around 60 kDa.
Structural, biochemical, and biophysical studies have shown how proteins interact with GroEL, a protein-folding machine, and how ATP (a molecule that provides energy for many processes in cells) induces changes in GroEL's shape that allow it to switch between binding to proteins and folding them. Mutational analysis and cryo-EM studies (a type of imaging technique) have revealed that proteins primarily bind to a specific part of GroEL, and that multiple parts of GroEL bind to the protein at the same time. This binding causes the parts of GroEL to extend and expand, which helps to unfold the protein. Additionally, the protein's binding to GroEL provides a mechanical load on GroEL, which helps to further unfold the protein. Finally, when ATP is added, the parts of GroEL rotate, which removes the binding sites from the inside of the chamber and traps the protein in the chamber, which is now capped by GroES (another protein-folding machine). Group 2 #chaperonins are similar to GroEL, but have a slightly different structure. They are found in both eukaryotes (organisms with a nucleus, like humans) and archaea (a type of single-celled organism). They form back-to-back rings and have a high degree of sequence identity/similarity to GroEL. The main difference is an extension in the part of GroEL that forms the lid of the folding chamber. This extension helps to further unfold the protein.
The structural similarities between the Group 2 chaperonins and GroEL, both essential for folding proteins. Group 2 chaperonins have 8- or 9-fold symmetry, meaning that they form back-to-back rings with the same domain structure and a high degree of sequence identity/similarity to GroEL. The main difference between the two is an extension in the helix H equivalent in the apical domain of the Group 2 chaperonin, which removes the need for a GroES co-chaperone. Structural studies of the Group 2 chaperonins in different nucleotide bound states have revealed open, substrate binding and closed, substrate folding conformations similar to GroEL. These conformations involve a large clockwise twist of the apical domains and an inward tilt of the whole subunit, which brings the catalytic Asp in the intermediate domain close to the ATP binding site and closes the folding chamber. The ring expansion/contraction of Group 2 chaperonins is facilitated by the 1:1 nature of their inter-ring interface, allowing the equatorial domains to move more freely than in GroEL.
ATP-driven chaperones are proteins that help other proteins maintain their structure and function. They do this by binding, unfolding, refolding, and disaggregating proteins that are not in their native state. The Hsp70 system uses ATP binding and hydrolysis to regulate the binding and release of substrates. It is also regulated by co-chaperones. Hsp90 uses its ATPase cycle to induce multiple conformations that bind and stabilize or help mature the substrate proteins. It is also regulated by co-chaperones. The Hsp100s use ATP to unfold, thread, and disaggregate substrate proteins. In ATP-dependent proteolysis, the unfoldase is connected to a protease which breaks down the unfolded substrate proteins. The disaggregases, in combination with the Hsp70 system, use ATP-induced conformational changes to disaggregate and unfold substrate proteins. GroEL-GroES uses ATP binding to induce conformational changes to convert from a substrate binding to a substrate folding complex. It may also use the ATP-induced conformational changes to force the substrate to unfold. GroES binding then ejects the substrate from the binding surface, giving it a chance to fold in isolation during the slow ATP hydrolysis step. The archaeal Group 2 chaperonins use ATP-induced domain rotations that are similar to GroEL, but the conformational changes are not in the same order. The eukaryotic cytosol Group 2 chaperonin is similar to the archaeal system, but its ATPase cycle and action appear to be more complex and specific to the substrate.
In conclusion, ATP-driven chaperones are proteins that help other proteins maintain their structure and function by binding, unfolding, refolding, and disaggregating proteins that are not in their native state. Structural studies of GroEL and Group 2 chaperonins have revealed ATP-induced conformational changes that bind, unfold, and refold proteins in the ATP-dependent folding process. GroEL uses ATP binding to induce a conformational change that switches between the substrate binding and substrate folding states. The archaeal Group 2 chaperonins have a similar mechanism, but with a different order of conformational changes. The eukaryotic cytosol Group 2 chaperonin is more complex, indicating different substrate-specific functions. In general, ATP-driven chaperones help to ensure the proper folding of proteins and support the lifecycle of proteins.
