Bifunctional peptide targets CXCR4 drug-resistant cancer stem cells to fight resistance to conventional chemotherapy

Jul 30, 2018 3:00:00 PM

Ovarian cancer (OVC) patients often acquire resistance to cytotoxic drugs such as cisplatin, doxorubicin, and paclitaxel within a year, leading to a disease recurrence rate of up to 80%. Hyun Hee Lee and colleagues at Weill Cornell Medicine, New York, USA have used a peptide to target the G-protein coupled receptor 4 (CXCR4) that plays a significant role in promoting tumorigenesis and drug resistance. The research team has shown that targeting a CXCR4High cancer stem cell population with a selective peptide resulted in a synergistic cytotoxic effect when combined with chemotherapy agents such as doxorubicin and cisplatin. This is a promising approach in fighting drug resistance and improving treatment outcomes.

Read More

Topics: Peptide synthesis, PS3 peptide synthesizer, CXCR4-KLA peptide, Ovarian cancer, cytotoxic drug resistance

A peptide targeting FGFR2 receptor promises early detection of esophageal adenocarcinoma

Jun 28, 2018 10:00:00 AM

The incidence of esophageal adenocarcinoma (EAC) is rapidly increasing, with 450,000 new cases diagnosed and 400,000 deaths reported annually worldwide. Early detection is complicated by difficulty in detecting the flat premalignant lesions. However, the overexpression of cell surface fibroblast growth factor receptor 2 (FGFR2) is an early event in disease progression. A team comprising researchers based at the University of Michigan, USA and The Fourth Military Medical University, China, have identified a peptide that binds with high specificity to the extracellular domain of FGFR2, making this peptide a promising clinical imaging agent for early detection of esophageal adenocarcinoma.

Read More

Topics: Peptide synthesis, PS3 peptide synthesizer, FGFR2 receptor, esophageal adenocarcinoma, Clinical imaging agent, Cancer

Mapping neuropeptide-receptor and agonist binding: peptide synthesis strategies to guide the design of novel modulators of appetite regulation

May 8, 2018 9:00:00 AM

With 30–70% of adults in the European Union designated overweight and 10–30% obese (WHO), and more than one third of US adults obese (CDC), the global obesity epidemic has stimulated much research into the fundamentals of appetite regulation. Bo Xu and colleagues, based at Uppsala University in Sweden and collaborating with Novo Nordisk A/S in Denmark, have studied the interaction between the agonist neuropeptide Y (NPY) and the human receptor Y2 involved in appetite regulation. Using a combination of computational modeling, peptide chemistry and in vitro pharmacology analysis the research team has gained insight into interactions that promise to guide the design of novel modulators to fight obesity.

Read More

Topics: Prelude x, Peptide synthesis, Obesity, Human neuropeptide Y, NPY, Appetite regulation

Inhibitory peptides help identify receptor complex vital to male fertility

Mar 12, 2018 9:00:00 AM

The acrosome reaction is critical for the sperm to penetrate the female egg and fertilize it. Progesterone plays a key role in the acrosome reaction, but how this works has been unclear since spermatozoa lack classical progesterone receptors. Wenming Xu and collaborators at Sichuan University, China, The Chinese University of Hong Kong, and the Australian National University, have shown that the progesterone-induced Ca2+ influx required for the acrosome reaction involves the progesterone receptor or modulator, gamma-aminobutyric acid type A (GABAA) receptor delta subunit (GABRD), in combination with the P2X2 receptor.
The first confirmation that delta subunits were involved in the Ca2+influx came with an experiment that demonstrated that increased intracellular levels of Ca2+ in spermatozoa after progesterone stimulation were suppressed by the δ(392-422) inhibitory peptide but unaffected by a scrambled δ control peptide or a Υ2-peptide.

Read More

Topics: Peptide synthesis, Symphony X peptide synthesizer, Male fertility, The acrosome reaction, Inhibitory 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. 

Read More

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

Enabling identification of phosphorylated cysteine: Novel chemoselective synthetic and analytical methods

Dec 5, 2017 10:32:31 AM

Protein phosphorylation plays a key role in the regulation of signaling pathways and many other cellular processes. Studies of phosphorylation have focused on serine, threonine and tyrosine amino-acid side chains, while the phosphorylation of other amino acids, such as phospho-histidine (pHis), -arginine (pArg), -lysine (pLys) and -cysteine (pCys), is less well understood. Studies have been hindered by technical limitations, primarily acid lability. To address this problem, Jordi Bertran-Vicente and colleagues have developed a novel chemoselective and stereochemically defined phosphorylation strategy for Cys residues.  The method employs the nucleophilic reactivity of P(III)-reagents (phosphites) with electrophilic disulfides. The research team has also developed a mass spectrometry-based proteomic approach to identify and characterize pCys sites that naturally occur in peptides. 

Read More

Topics: Peptide synthesis, Tribute, Tribute peptide synthesizer, pCys, Protein phosphorylation

Green Chemistry: healthier chemists with every peptide synthesized

Sep 27, 2017 3:00:00 PM

As solid phase peptide synthesis (SPPS) typically uses an excess of reagents to drive the completion of these reactions, there is a need for the use of a large amount of solvents, most of which are hazardous. In fact, solvents make up the major component of the reaction mixture representing 80−90% of the nonaqueous mass, as concluded in a survey by GSK in 2007 about the materials used for the manufacturing of active pharmaceutical ingredients (APIs). Benzotriazols (and variants) are frequently used as coupling agents for peptide syntheses in the pharmaceutical industry. However, their safety profile must be carefully considered as these compounds display explosive properties, when heated under defined confinement or when subjected to mechanical stimulus that leads to restrictions for their shipping and handling. In addition, a variety of allergic responses have been reported from exposure to some coupling agents. Moreover, residues of the starting material 1-Chloro-2-nitrobenzene and hydrazine, used for the synthesis of bezotriazol moieties are known to have toxic effects, even at parts per billion (ppb) levels. For example, irritating effects on the mucous membrane, as well as skin irritation, have been reported when exposed to the dust of HOBt.


Taking into consideration the hazardous potential of the essential benzotriazole-based coupling reagents, our partner Luxembourg Biotechnologies Ltd. decided to reduce the environmental and health impact of these chemicals by developing compounds that are safer yet achieve comparable results as HOBt. With these compounds we move towards our goals to create a healthy and safe working environment and achieve a zero-disaster risk that is implemented in local policies, training, lab goal setting, and performance evaluation.

Read More

Topics: Peptide synthesis, solid-phase peptide synthesis, green chemistry, Oxyma-based reagents

Multifunctional thermoresponsive peptide hydrogels designed to meet the demands of biomedical applications

Sep 6, 2017 10:00:00 AM

The uncertainties of the long-term stability and effects of artificial materials in the human body have stimulated research into more natural materials for many biomedical applications. This search has lead to the discovery of peptide hydrogels, a highly promising family of constructs that are capable of self-assembly, typically into β-sheets, and can emulate the properties of natural materials such as collagen. Fine-tuning the mechanical properties of hydrogels to solve biomedical problems is, however, a real challenge. A team headed by researchers at the University of Auckland in New Zealand has come one step further with peptide hydrogels that are reversibly thermoresponsive. Their innovative hydrogels are based on multifunctional peptides that combine a hydrogel-forming β-sheet peptide segment, an enzyme substrate that enables biodegradation, and a RGD sequence to promote cell adhesion.

Read More

Topics: Peptide synthesis, PS3 peptide synthesizer, Peptide synthesizer, β-sheet-forming peptides, Multifunctional peptides, Hydrogel

The CWR tripeptide - a promising activator of SIRT1 in the fight against Alzheimer’s disease

Aug 10, 2017 3:00:00 PM

The list of scientific publications by users of our peptide synthesizers is growing steadily.This review article is based on a recent article in the European Journal of Medicinal Chemistry by Rahul Kumar and colleagues at All India Institute of Medical Sciences and School of Computational and Integrative Sciences, Jawaharlal Nehru University in New Delhi, India.

In this study, Rahul Kumar and his colleagues designed and synthesized a novel peptide SIRT1 activator. SIRT1 has been shown to have a protective role against Alzheimer's disease.The peptide, CWR, was tested for its effect on the activity of recombinant SIRT1 protein and also determining its cytotoxicity. CWR was found to be a potent allosteric activator of SIRT1 both by molecular docking and in vitro analysis, increased cell viability and no toxicity to human erythrocytes were also observed.

Read More

Topics: Peptide synthesis, PS3 peptide synthesizer, Alzheimer's disease, SIRT1 activator

Designer peptoids-improving on Mother Nature

Jul 27, 2017 10:00:00 AM

Peptoids offer a way of improving on nature in a range of biomedical applications such as antimicrobial agents, nanomaterials and diagnosis and treatment of a wide number of cancers.Over 150 peptoid-related papers are now being published per year, and in total, there are over 1700 publications.

Read More

Topics: Peptide synthesis, Peptoids, Symphony X peptide synthesizer