作者: Heberling, Matthew M ; de Wildeman, Stefaan ; Postema, Christiaan P ; Janssen, Dick B ; Wijma, Hein J ; Crismaru, Ciprian G ; Szymanski, Wiktor ; Otzen, Marleen

Pseudomonas species strain SBV1 can rapidly grow on medium containing β-valine as a sole nitrogen source. The tertiary amine feature of β-valine prevents direct deamination reactions catalyzed by aminotransferases, amino acid dehydrogenases, and amino acid oxidases. However, lyase- or aminomutase-mediated conversions would be possible. To identify enzymes involved in the degradation of β-valine, a PsSBV1 gene library was prepared and used to complement the β-valine growth deficiency of a closely related Pseudomonas strain. This resulted in the identification of a gene encoding β-valinyl-coenzyme A ligase (BvaA) and two genes encoding β-valinyl-CoA ammonia lyases (BvaB1 and BvaB2). The BvaA protein demonstrated high sequence identity to several known phenylacetate CoA ligases. Purified BvaA enzyme did not convert phenyl acetic acid but was able to activate β-valine in an adenosine triphosphate (ATP)- and CoA-dependent manner. The substrate range of the enzyme appears to be narrow, converting only β-valine and to a lesser extent, 3-aminobutyrate and β-alanine. Characterization of BvaB1 and BvaB2 revealed that both enzymes were able to deaminate β-valinyl-CoA to produce 3-methylcrotonyl-CoA, a common intermediate in the leucine degradation pathway. Interestingly, BvaB1 and BvaB2 demonstrated no significant sequence identity to known CoA-dependent ammonia lyases, suggesting they belong to a new family of enzymes. BLAST searches revealed that BvaB1 and BvaB2 show high sequence identity to each other and to several enoyl-CoA hydratases, a class of enzymes that catalyze a similar reaction with water instead of amine as the leaving group.

2010-05-21·Organic Process Research & Development

Rapid Identification of a Scalable Catalyst for the Asymmetric Hydrogenation of a Sterically Demanding Aryl Enamide

作者: Boogers, Jeroen A. F. ; Janssen, John ; Straatman, Harrie ; Kuilman, Thijs ; Vijn, Robert Jan ; de Vries, Johannes G. ; de Vries, Andre H. M. ; Lefort, Laurent

High throughput screening was used to find a cost-effective and scalable catalyst for the asym. hydrogenation of a sterically demanding enamide as an intermediate towards a new potent melanocortin receptor agonist useful in the treatment of obesity.Lessons drawn from the testing of a 1st library of 96 chiral monodentate phosphoramidites led to the design of a 2nd focused library of 16 chiral ligands, allowing the discovery of a new efficient catalyst.This catalyst was based on Rh and a bulky monodentate phosphite ligand.The catalyst was scaled up and used in the kilogram production of the desired bulky chiral amide.

2009-08-10·Chemistry – A European Journal2区 · 化学

Is the Backbone Conformation of C^α‐Methyl Proline Restricted to a Single Region?

2区 · 化学

Article

作者: Toniolo, Claudio ; Formaggio, Fernando ; Peggion, Cristina ; Crisma, Marco ; Kaptein, Bernard ; Moretto, Alessandro ; De Poli, Matteo ; Broxterman, Quirinus B

AbstractCα‐Methyl‐L‐proline, orL‐(αMe)Pro, is probably the most conformationally constrained α‐amino acid. In particular, itsωandϕtorsion angles are restricted to about 180 and −60°, respectively, and only three ranges of values are theoretically available forψin mono‐ or longer peptides, namely, about −30° (cis′, 310/α‐helical structure), 60° (inverse γ turn), or 140° (trans′, poly(L‐Pro)n II structure). In this work, we examined the tendency of a number of Nα‐acyl dipeptide N′‐alkylamides of the type RCO‐(αMe)Pro‐Xxx‐NHR′ or RCO‐Xxx‐(αMe)Pro‐NHR′, in which Xxx isL(orD)‐Ala, Aib (α‐aminoisoburyric acid), orL(orD)‐(αMe)Pro, long enough to fold into intramolecularly hydrogen‐bonded γ or β turns. The results are compared with those obtained for the corresponding dipeptides based on Pro, a well‐known turn‐forming residue. For the crystal‐state 3D‐structural analysis we used X‐ray diffraction, whereas our solution conformational analysis was heavily based on the FTIR absorption and1H and13C NMR spectroscopy techniques. We conclude that (αMe)Pro is able to explore bothtrans′andcis′ ψareas of the conformational space, but in (αMe)Pro the latter is overwhelmingly more populated, in marked contrast to the Pro preference. This finding is a clear indication that in (αMe)Pro the major 3D‐structural determinant is the Cα‐methyl group. The circular dichroism (CD) signature of a peptide type III′ β‐turn conformation is also proposed.

项与 DSM Pharmaceutical Products, Inc. 相关的新闻（医药）

2023-11-28

·BioSpace

Belhaven Biopharma Achieves Significant Milestones in Advancing Nasdepi - a Revolutionary Nasal Dry Powder Epinephrine Product

Several key accomplishments completed to finish 2023 and create a strong foundation for 2024. RALEIGH, NC / ACCESSWIRE / November 28, 2023 / Belhaven Biopharma, a pioneering force in the development of emergency-use epinephrine for the 21st century, proudly announces new Board of Director appointments and the initiation of a first in human clinical trial that positions the company as a novel alternative in the $2.5 billion U.S. epinephrine market. Belhaven Biopharma is thrilled to announce the addition of three distinguished industry leaders to its board, enhancing the company's strategic vision. Dr. Eric Edwards, MD, PhD, currently the co-founder and CEO of Phlow Corporation, brings invaluable expertise to Belhaven with impactful contributions to the allergy field. As the Chief Medical Officer, VP of Innovation and R&D, and co-founder of Kaléo, Inc., he played a pivotal role in the development of novel medicines, including the widely used AUVI-Q epinephrine auto-injector. Dr. Edwards' extensive experience in pharmaceutical innovation and patient advocacy aligns seamlessly with Belhaven's mission. Wes Wheeler, Former President of Global Healthcare at UPS, has an impressive 40-year career spanning various leadership roles at GlaxoWelcome (now GSK), Valeant, Patheon, and DSM Pharma. With a track record of transforming companies and diverse experience in manufacturing, drug development, and supply chain logistics, Wes Wheeler brings a wealth of operational knowledge to guide Belhaven's strategic growth. Dr. Derek M. Winstanly, MBChB, with a distinguished career in biopharmaceuticals, currently leads as Board Chair of Renovion and serves on the Board of Huya. His expertise, honed at Quintiles Transnational as EVP and Chief Customer and Governance Officer, encompasses government affairs, compliance, and medical strategy. A former executive at GlaxoWelcome (now GSK), Dr. Winstanly's extensive experience spans clinical development to global commercial strategy while President of Nippon Wellcome, now Glaxo-SmithKline K.K., in Japan. According to CEO Scott Lyman, "We are confident that the addition of these esteemed board members will significantly contribute to the company's vision of modernizing the delivery of emergency use medicines and our goal of increasing patient access to these medicines globally." In addition to their new board members, building on the success of a $3 million Bridge Round closing this December, Belhaven Biopharma is announcing a new funding round starting in January 2024. This upcoming Series A Round will fund this initial program to FDA approval and preparation for commercial launch of Nasdepi. Belhaven Biopharma is enthusiastic about the continued support from its current investors and the strategic use of funds to advance Nasdepi through clinical development. Lastly, Belhaven Biopharma is excited to announce the initiation of the first-in-human clinical trial for Nasdepi, scheduled to conclude this December. This critical milestone marks a significant inflection point towards bringing the first dry powder nasal epinephrine to market, offering a user-friendly and efficient solution for emergency use. These milestones underscore the company's commitment to improving accessibility, safety, and efficacy in the treatment of anaphylaxis. About Belhaven Biopharma Belhaven Biopharma is a pharmaceutical research company specialized in developing life-saving medications delivered quickly, effectively, and painlessly with a simple, dry powder, single-use nasal device. They are at the forefront of developing nasal dry powder epinephrine, which is revolutionizing emergency-use epinephrine delivery and expanding global access. Nasdepi is Belhaven's lead program is being developed to treat life-threatening allergic reactions including anaphylaxis in people who are at risk for or have a history of serious allergic reactions. Contact Information Sophia Lange PR sophia@ascendantgroupbranding.com 6047892465 SOURCE: Belhaven Biopharma View source version on accesswire.com:

高管变更

2011-06-28

·BioSpace

DSM Biologics Expands its Innovative Biomanufacturing Technology Portfolio With the Introduction of the New Kremer Method™

PARSIPPANY, N.J., June 28, 2011 /PRNewswire/ -- Royal DSM, the global Life Sciences and Materials Sciences company, today announced the introduction of the Kremer Method, an innovative proprietary technology developed by DSM scientists which improves downstream processing of monoclonal antibodies (mAbs) for faster and more cost effective production of biopharmaceuticals. The Kremer Method reduces processing and preparation times, labor and materials requirements and cost of goods for a more sustainable manufacturing platform. DSM provides and develops technologies for optimizing mammalian cell culture processes. Examples are the proprietary XD® Technology for use with mammalian cell lines. The XD® process creates very high cell densities within the bioreactor, resulting in significant output enhancements of 5-15 fold using commercially available equipment. In the downstream processing area, DSM's proprietary Rhobust® technology is the next generation in expanded bed chromatography (EBA), using cross linked agarose beads with Tungsten Carbide to increase the particle density. Rhobust® is applied as a direct capture and clarification step for mammalian and microbial harvest to increase yields, reduce the number of unit operations and reduce process cost. The new Kremer Method further optimizes the downstream processing of proteins and monoclonal antibodies. Karen King, President of DSM Biologics, a business unit of DSM Pharmaceutical Products, commented: "DSM is continually innovating to advance the world of biopharmaceutical manufacturing to the next level. We are pleased to announce the introduction of the new DSP optimization technology, the Kremer Method. The combination of the Kremer Method with our other proprietary technologies significantly reduces the overall costs and processing times of biopharmaceuticals while maintaining high product quality." Rolf Douwenga, Vice President of Global R&D for DSM Biologics explained: "The Kremer Method is a valuable addition to the platform of DSM's technologies addressing the full range of mammalian cell culture systems for protein and monoclonal antibody production. The method uses in-line dilution to streamline the purification and polishing of mAbs into one single continuous step in a flow-through mode. This eliminates the need for storage and reduces the amount of material usage such as buffers and resins. The Kremer Method reduces processing and preparation times, labor requirements and the cost of goods and presents an ideal solution to achieving cost effective processing." After the capture step in conventional downstream processes, further purification and polishing of proteins are traditionally carried out as two separate batch unit operations. With the Kremer Method these steps are streamlined to work as one single unit operation. Using this method; Host Cell Proteins (HCP's) were removed to a level below the limits of detection; complete aggregate removal was observed comparable to current state of the art processes; and recoveries of 90% were achieved. Several patent applications have already been XD® is a registered trademark of DSM Rhobust® is a registered trademark of DSM DSM Bright Science. Brighter Living. DSM Pharmaceutical Products is a Business Group of Royal DSM N.V., a global science-based company active in health, nutrition and materials. By connecting its unique competences in Life Sciences and Materials Sciences DSM is driving economic prosperity, environmental progress and social advances to create sustainable value for all stakeholders. DSM delivers innovative solutions that nourish, protect and improve performance in global markets such as food and dietary supplements, personal care, feed, pharmaceuticals, medical devices, automotive, paints, electrical and electronics, life protection, alternative energy and bio-based materials. DSM's 22,000 employees deliver annual net sales of about euro 9 billion. The company is listed on NYSE Euronext. More information can be found at and .For more information: Karen KingRolf DouwengaPresident, DSM BiologicsVice President of Global R&D, DSM Biologics+1 973 257 8220Tel: +1 973 257 8220karen.king@dsm.com rolf.douwenga@dsm.com Forward-looking statements This press release may contain forward-looking statements with respect to DSM's future (financial) performance and position. Such statements are based on current expectations, estimates and projections of DSM and information currently available to the company. DSM cautions readers that such statements involve certain risks and uncertainties that are difficult to predict and therefore it should be understood that many factors can cause actual performance and position to differ materially from these statements. DSM has no obligation to update the statements contained in this press release, unless required by law. The English language version of the press release is leading. SOURCE DSM

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