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Note: As of September 30th there will be order processing and shipment delays that may last until October 8, 2020 as we are transitioning to a new ERP system. Please email to discuss what accommodations we can provide during this time.

Designing peptides to meet the challenge of the next generation of druggable targets

Jul 30, 2020 9:49:00 AM

Targeting protein–protein interactions (PPIs) is a new challenge in expanding druggable space. Cyclic peptides show promise in targeting PPIs and to better understand their structure–activity relationships a research team at Tufts University, USA, has analyzed a series of designed, well-structured cyclic hexapeptides and use simulations and experimental techniques to understand their global structural ensembles. They discovered a previously unappreciated role for β-branched residues in stabilizing specific conformations of cyclic hexapeptides, and their approach shows promise in the prediction of structure–activity relationships for drug development. Their work was rewarded by being on the front cover of Biophysical Journal, Volume 116, Issue 3.

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Topics: Peptide synthesis, Protein-Protein Interactions (PPIs), Tribute peptide synthesizer, Cyclic peptides

Peptide inhibitor of methylation casts new light on epigenetic-based cancer therapy

Jul 1, 2020 12:00:00 AM

The first peptide-derived epigenetic drug (Romidepsin) was approved in 2009 for the treatment of cutaneous T cell lymphomas (CTCL), and in 2011 for peripheral T cell lymphomas (PTCL) (2). Romidepsin also has potential in the treatment of other kinds of cancer, lung fibrosis, and Epstein-Barr infections. Currently, it is the only FDA-approved peptide medicine specifically designed to target epigenetic effects. Nesiritide, a peptide originally approved in 2001 for the symptomatic treatment of acute decompensated heart failure due to its vasodilating activity has since been repurposed due to its epigenetic effects. These peptides are not yet approved in the European Union by the EMA.

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Topics: Prelude, Peptide synthesis, Protein-Protein Interactions (PPIs), Peptide synthesizer, Cyclic peptides

Peptide drug leads with increased inhibitory properties synthesized using a divergent strategy

Feb 6, 2018 2:01:22 PM

Protein-protein interactions (PPI) play a major role in regulating many cellular processes, which makes them attractive druggable targets. The large surface area involved in PPIs, however, demands high selectivity of large drug leads such as proteins that can be difficult to modify and fine-tune. To demonstrate a solution to this problem, Christian Tornøe and his colleagues at Novo Nordisk in Denmark have synthesized analogues of Bowman-Birk protease inhibitor (BBI) by using native chemical ligation of peptide hydrazides to link together peptide building blocks to generate several analogues of BBI. This approach required fewer reaction steps than a linear synthesis strategy, and could be used to graft a specific region of a potent trypsin inhibitor onto the α- chymotrypsin-binding loop of BBI that boosted its inhibitory effect four-fold. 

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Topics: Peptide synthesis, Protein-Protein Interactions (PPIs), Prelude peptide synthesizer

Advancing drug targets for peptide-peptide interactions: Peptide flexibility is key in inhibiting the MDM2/p53 interaction

Jun 26, 2017 2:00:00 PM

The search for new drug classes has gone beyond the classically druggable genome, which appears to be limited to around 1,500 proteins. One route is the development of molecules that interfere with the Protein-Protein Interactions (PPIs) that are critical to all cellular processes, such as the regulation of cell growth, DNA replication, transcriptional activation, protein folding, and transmembrane signaling. One PPI-based drug target that involves a well-defined secondary structure is the interaction between the p53 tumor suppressor, the so-called “guardian of the genome” involved in programmed cell death, and MDM2, an important negative regulator of p53. This interaction involves a “hot spot triad” of three residues, Phe19, Trp23 and Leu26, on one face of the α-helical region of p53. Mimicking this region with a peptide became the focus of a collaborative effort between University of Gothenburg, Sweden and St. Jude Children’s Research Hospital in Tennessee, USA and resulted in key insights into the balanced peptide design required to achieve effective PPI inhibition (Danelius et al, 2016).

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Topics: Peptide synthesis, PS3 peptide synthesizer, Protein-Protein Interactions (PPIs), peptide-based PPI inhibitors