Exploring the Role of Methylated Peptides in Histone Methylation: A LifeTein Perspective

cell-penetration-peptide
cell-penetration-peptide

Histone methylation, a process that can signal either transcriptional repression or activation, is increasingly recognized for its interrelation with DNA methylation in mammals. For instance, the targeting of DNA methylation is intricately linked to H3K9 methylation, a key regulatory mechanism in gene expression. The p53 gene, known as the guardian of the genome and frequently mutated in human cancers, is regulated by various PTMs, including methylation.

Post-translational modifications (PTMs) of histone proteins, such as acetylation, methylation, and phosphorylation, are pivotal in regulating chromatin dynamics. Among these, the role of methylation, particularly at arginine or lysine residues, stands out for its complexity and significance. LifeTein, a leader in peptide synthesis, has contributed significantly to this field by synthesizing mono-, di-, or tri-methylated peptides. These peptides are instrumental in studying protein-protein interactions, especially in the context of histone methylation.

LifeTein’s contribution to this research is highlighted in a study focusing on the ASHH2 CW domain, which recognizes the methylation state at lysine 4 of histone 3 N-terminal tails. This domain is crucial in recruiting the ASHH2 methyltransferase enzyme to histones. The study utilized H3 histone tail mimicking peptides, specifically monomethylated (ARTK(me1)QTAR), dimethylated (ARTK(me2)QTAR), and trimethylated (ARTK(me3)QTAR) peptides, all synthesized by LifeTein with a remarkable 95% purity as confirmed by mass spectrometry.

The research documented the assignment of a shortened ASHH2 CW construct, CW42, which showed similar binding affinity and better expression yields than previous constructs. This advancement is significant in understanding how different methylation states affect protein-peptide interactions. The study also performed 1H–15N HSQC-monitored titrations to determine the saturation point of the protein-peptide complex. The findings revealed that the CW42 domain, when bound to the monomethylated histone tail mimic, showed similar perturbations in shifts as the di- and tri-methylated instances.

In summary, LifeTein’s synthetic methylated peptides have been instrumental in advancing our understanding of histone methylation. Their high-purity peptides have enabled researchers to delve deeper into chromatin dynamics and gene regulation complexities, paving the way for future discoveries in epigenetic therapies and cancer treatment.

Read the full article on SpringerLink](https://link.springer.com/article/10.1007/s12104-018-9811-x) for more detailed insights into this groundbreaking research.

Advancing Cancer Treatment with LifeTein’s Peptide Synthesis in Antibody Therapy

LifeTein’s Role in Overcoming Cetuximab Resistance in Colorectal Cancer

In the ongoing battle against cancer, monoclonal antibody therapies have emerged as a beacon of hope. Cetuximab, a therapeutic monoclonal antibody, has been developed to halt tumor growth by targeting the extracellular domain of the Epidermal Growth Factor Receptor (EGFR) on cancer cells’ surfaces. However, the emergence of resistance to cetuximab in clinical settings has posed a significant challenge.

Researchers have made a breakthrough using peptides synthesized by LifeTein to address this critical issue. By incorporating methylated arginine residues into these peptides, scientists successfully generated specific antibodies in mice. This innovative approach led to the discovery that Arg198 and Arg200 of EGFR undergo methylation by protein arginine methyltransferase 1 (PRMT1) in colorectal cancer cells. This methylation is now understood to be a key factor in the development of resistance to cetuximab.

The findings, published in the Journal of Clinical Investigation (2015;125(12):4529-4543. doi:10.1172/JCI82826), highlight the potential of PRMT1-mediated methylation of the EGF receptor as a target for overcoming cetuximab resistance. This research paves the way for developing more effective treatments for cancer patients, marking a significant advancement in the field.

LifeTein’s Comprehensive Peptide Synthesis Services

LifeTein’s contribution to this groundbreaking research is part of their broader commitment to advancing scientific discovery through their peptide synthesis services. Their offerings include:

  • COVID-19 Services & Products: Addressing the urgent needs of the pandemic.
  • Custom Antibody Services: Tailored solutions for specific research needs.
  • Rush Peptide Synthesis: Accelerated synthesis for time-sensitive projects.
  • Peptide Nucleic Acids (PNAs): Offering versatility in genetic research.
  • Custom Peptide Synthesis Services: Expertise in synthesizing complex peptides.
  • Gene Synthesis Service: Advanced techniques for precise gene construction.
  • Custom Chemical Synthesis: Broadening the scope of molecular innovation.

Exploring Other Innovations by LifeTein

LifeTein is not just limited to cancer research. Their expertise in peptide synthesis has led to various other significant contributions in the biomedical field:

  • Nanoparticles Enhanced by Cell-Permeable Peptides: LifeTein’s peptides are instrumental in improving the delivery and efficacy of nanoparticles in therapeutic applications.
  • Predicting Type 1 Diabetes in Children: Leveraging peptide technology, LifeTein is at the forefront of developing predictive tools for early detection of type 1 diabetes in pediatric populations.
  • Targeting Peritoneal Carcinomatosis with iRGD Peptide: The tumor-permeable peptide iRGD, synthesized by LifeTein, is a promising agent in targeting peritoneal carcinomatosis, enhancing drug delivery to tumor sites.
  • Simplifying and Enhancing Biosensors: LifeTein’s peptides play a crucial role in developing simpler, more efficient biosensors, pushing the boundaries of diagnostic technology.
  • Innovative Patents Using Peptides: LifeTein’s cutting-edge research has led to new patents in peptide-based technologies, showcasing their commitment to innovation and scientific advancement.

LifeTein’s pivotal role in overcoming cetuximab resistance in colorectal cancer is a testament to its expertise in peptide synthesis and its applications in medical research. Their diverse range of services and contributions to various fields underscore their commitment to advancing scientific knowledge and developing solutions for pressing health challenges. As LifeTein continues to explore the frontiers of peptide synthesis, their work not only illuminates the path to better cancer treatments but also opens doors to new possibilities in biomedical research and therapeutics.