How does the amino acid sequence of a protein chain determine and remain its 3D folded state? How do small proteins fold?
Many small proteins or miniproteins are peptides shorter than 40-50 residues with stable folding that contain secondary structure elements such as alpha helices and beta strands.
An autonomously folding, 35 residue, thermostable subdomain (HP36) of the villin headpiece, is the smallest folded domain of a naturally occurring protein. So, polypeptides simplify the protein-folding problem. It allows in-depth examinations of sequence-structure-stability relationships without using the complex larger proteins.
In this recent study, Rocklin et al. designed sequences intended to fold into desired structures. The novel proteins may be useful in bioengineering or pharmacological applications.
LifeTein is unveiling an expedited peptide synthesis program, promising to place peptides in its customers’ hands within 3-5 business days. The RushPep™ peptide synthesis service was designed to circumvent the existing limitations of conventional solid-phase peptide synthesis (SPPS), which involves a long coupling time and low yield. RushPep™ shortens the time needed for individual coupling, deprotection and washing steps. The proprietary methodology renders processing ten times faster than in classical synthesis while simultaneously circumventing the limitations caused by the formation of by-products or intermediates to which traditional SPPS approaches are subject.
“When designing the RushPep™ methodology, our focus was to not only to produce peptides of high quality and purity but also to offer a streamlined solution that would increase the efficiency of researchers’ protein discovery workflows,” stated Dr. Ya Chen, Head of LifeTein’s Rush Peptide Synthesis Group. “RushPep™ achieves these goals by synthesizing the peptides in 3–5 business days to accelerate research and discovery.”
Chen continued, “The reliability of RushPep™ rush peptide synthesis ensures that the peptides are finished in 3–5 business days with high-batch-to-batch reproducibility. ” Most of the crude peptides have a purity of over 80%. RushPep™ peptide service is valuable for the scientists and researchers because it allows them to finish their proteomics projects in a fast and cost-efficient manner.
All peptides used in this study for Parkinson’s disease were synthesized by LifeTein. The α-synuclein is an indication in the pathogenesis of Parkinson’s disease. It was found that a molecular mimicry mechanism between HSV1 and human α-synuclein could trigger PD.
Biotinylated wild-type and modified (pT27 and T27W) ID2 peptides (amino acids 14–34) were synthesized by LifeTein. ID2 binds to the VHL ubiquitin ligase complex.This ID2 peptide could be used to inhibit tumour growth for patients with glioblastoma.
Peptide library is increasingly used to define antibody epitopes and substrate specificities of protein kinases. For epitope mapping, overlapping peptides are made to span the antigenic protein sequence. The antigenic determinant recognized by a monoclonal antibody can then be screened and defined. The alanine scanning method can also be used to assess that residue’s contribution to antibody binding and to determine which substitutions affect antibody recognition (mutational analysis). Unrelated synthetic peptides can be used to evaluate the antibody cross-reactivity.
Overlapping peptides from LifeTein were used to map the region of Fragment 3 by epitope mapping of anti-Fzd2 antibody. This anti-Fzd2 antibody was found to reduce tumor growth. Wnt signaling plays a critical role in colorectal cancer. Researchers found that Wnt receptor Frizzled2 (Fzd2) and its ligands Wnt5a/b are elevated in metastatic liver, lung, colon, and breast cancer cell lines. Their high level expression correlates with markers of epithelial-mesenchymal transition (EMT). By epitope mapping using synthetic peptides from LifeTein, the researchers mapped the epitope to a specific region. The antibody to Fzd2 was found to reduce cell migration and invasion. Targeting this pathway may provide a cure for patients with tumors expressing high amount of Fzd2 and Wnt5a/b.
We have developed an antibody to Fzd2 that reduces cell migration and invasion and inhibits tumor growth and metastasis in xenografts. We propose that targeting this pathway could provide benefit for patients with tumors expressing high levels of Fzd2 and Wnt5a/b.
Cell-penetrating peptides (CPPs) such as the HIV TAT peptides are able to enter cell by direct translocation and endocytosis. Click here to see details about the CPP: http://lifetein.com/Cell_Penetrating_Peptides.html
Cell Penetrating Peptides
The following table shows a selection of currently known CPPs, their origins and sequences.
Currently, only two Food and Drug Administration (FDA) approved drugs for weight loss are available in the United States: the appetite suppressant phentermine and the inhibitor of fat absorption orlistat.
An MD Anderson group designed a new peptide drug: CKGGRAKDC-GG-D(KLAKLAK)2 (termed adipotide). This is a synthetic peptide that triggers cell death. These data showed that the peptide may be useful for treating obesity in humans.
Tthe MD Anderson group used a peptide library to screen and identify regions that bind to specific vascular cells. The interaction identified will be used as effective drugs to target particular protein functions.
This video explains factors that have contributed to the obesity epidemic.
Immune-based cancer treatments are one emerging type of therapy, and they show great potential. Synthetic-peptide-based vaccines, which are designed to elicit T cell immunity, are also a promising approach to the prevention and treatment of both infectious diseases and malignant disorders, such as cancer.