Synthetic Peptides as Protein Mimics in Biological Research

Synthetic Peptides as Protein Mimics

Synthetic peptides have proven an excellent type of molecule for the mimicry of protein sites. The modified peptides increase the proteolytic stability of the molecules, enhancing their utility for biological applications.

Toolbox for Peptide Synthesis: Non-Proteinogenic Amino Acids and Site-Selective Ligation

The long peptides can be synthesized by the ligation method. Amino acid derivatives with modified backbone length and side-chain orientation, such as d-amino acids, N-alkyl glycine monomers, or proteolytically stable amino acid derivatives can be introduced to the peptides.

Protein Secondary Structure Mimics: α-Helix Mimics, β-Sheet Mimics
Peptide chains can be organized into secondary structures, such as α-helices and β-sheets. Peptides that mimic α-helices and β-sheets of proteins are attractive targets for drug development and tools to explore protein binding mechanism.

The α-helical conformation of a peptide can be induced by adding covalent links between amino acid side chains at selected positions. These links can be formed by lactam and disulfide bridges, triazole-based linkages, and hydrocarbon staples.

In β-sheets, β-strands are connected via loops or turns. Methods to mimic turn structures include macrocyclization, dipeptide of d-proline and l-proline, or α-aminoisobutyric acid in combination with either a d-α-amino acid or an achiral α-amino acid. An example of stimuli-responsive peptides is the temperature-dependent formation of hydrogels by β-sheet peptides. The β-hairpin mimic undergoes gelation upon heating at 60°C, and is completely reversible while cooling.

Protein Mimics in Biomedical Research

Peptides mimicking the CHR region of gp41 were developed to inhibit the formation of the six-helical bundle. Peptides that mimic these receptors are useful tools to explore the details of virus infection mechanism, as well as to develop new drugs against HIV-1. Peptides that mimic the extracellular domains of seven transmembrane G protein-coupled receptors (GPCRs), which is composed of the N-terminus (NT) and the three extracellular loops (ECLs) were explored. Peptide Ac-RERF-NH2 has a high propensity to adopt an α-turn structure and could be a promising drug candidate against cancer.

The design of peptides as protein mimics has evolved as a promising strategy for the exploration of protein-protein interactions, as they are biocompatible, biodegradable, and functionally selective.

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

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.

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.

LifeTein’s contribution to this research is highlighted in a study focusing on the ASHH2 CW domain, which is responsible for recognizing 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 the complexities of chromatin dynamics and gene regulation, paving the way for future discoveries in epigenetic therapies and cancer treatment.

Read the full article on SpringerLink]( for more detailed insights into this groundbreaking research.

A New Patent Using Peptides

A patent has been published that describes new methods of manipulating plant stomatal development through artificially controlling how CRSP is expressing in plant cells.  The cleavage of epidermal patterning factor 2 (EPF2) by a serine protease CRSP is a key regulating mechanism in plant stomatal development.  A 30-mer EPF2 peptide, dual-tagged with DABCYL and EDANS, was synthesized by LifeTein to evaluate the protease activity of synthetic CRSP in a FRET assay.

New Patent Using Peptides Synthesized By LifeTein

Compositions and methods for mediating plant stomatal development in response to carbon dioxide and applications for engineering drought tolerance in plants.

Peptide Synthesis Home Page

Our Services:

COVID-19 Services & Products

Custom Antibody Services

Rush Peptide Synthesis

Peptide Nucleic Acids (PNAs)

Custom Peptide Synthesis Services

Gene Synthesis Service

Custom Chemical Synthesis

Other Posts:

Nanoparticles Get Help from Cell-Permeable Peptides

Predicting type 1 diabetes in children

Improving Antibody Therapy For Colorectal Cancer

A tumor-permeable peptide iRGD by LifeTein targets peritoneal carinomatosis

To Make Simpler and Better Biosensors