LifeTein, the peptide synthesis service company

2012-01-19T11:12:00.001-05:00

Cell-penetrating peptides (CPPs) cell entry mechanism updated: http://bit.ly/zwTQFx

Amino acid composition of cell-penetrating peptides

2012-01-19T11:10:00.001-05:00

Cell-penetrating peptides (CPPs) such as the HIV TAT peptides are able to enter cell by direct translocation and endocytosis. HIV TAT or even simple poly-arginines can be effectively designed for drug delivery. However how cell-penetrating peptides, HIV TAT peptide for example, accomplish these cellular molecular transfer has so far been a mystery.

How does simple HIV TAT peptide facilitate mechanisms like direct translocation and multiple endocytotic processes? Researchers from Gerard Wong’s lab found how HIV TAT peptides can have multiple interactions with the cell membrane, the actin cytoskeleton and specific cell-surface receptors to produce multiple pathways of translocation under different conditions. Click here for the publication from Gerard Wong’s lab: http://bit.ly/zQrH6t.

Interestingly, TAT peptide can multiplex different interactions with the same sequence, thus interacting with the membrane, the actin cytoskeleton, and specific receptors to produce multiple pathways of translocation under different conditions.

CPPs entry mechanism is sensitive to the peptide sequence. The addition of a single hydrophobic residue to purely hydrophilic CPPs can drastically modify the translocation mechanism. For example, polyarginine (polyR), the simplest prototypical CPP, can induce the cell membrane pore formation. Hydrophobic amino acids create positive curvature by inserting into the membrane. Arginine simultaneously creates positive and negative curvatures, whereas lysine creates negative curvature along one direction only. This implies a compensatory relation between arginines and lysines/hydrophobes.

Why is the hydrophobic content of the TAT peptide relatively low if hydrophobicity can help generate negative Gaussian curvature? CPPs use less hydrophobic residues to generate saddle-splay curvature. This difference in sequences can potentially only induce transient pore-like translocation structures in the membrane and thus lead to shorter pore lifetimes for CPPs. Because of the amino acid composition for CPPs, the TAT peptide can mediate endocytosis with or without receptors.

Order your cell penetrating peptide now: http://ping.fm/pd9n4

The following table shows a selection of currently known CPPs, their origins and sequences.

http://bit.ly/zwTQFx

Sex peptide on female reproductive behaviour

2011-12-27T15:29:00.001-05:00

Rafaeli lab used sex peptide, synthesized by LifeTein, to show that virgin females injected with Drosophila melanogaster SP (DrmSP), in addition to inhibition of pheromone production, also exhibited a suppression of calling behaviour and a significant reduction in the gene expression levels of the PBAN-receptor. http://bit.ly/pAxoWm

2011-12-27T15:27:00.001-05:00

Rafaeli lab used sex peptide, synthesized by LifeTein, to study the factors in the suppression of sex pheromone production after mating. http://bit.ly/pAxoWm

2011-12-16T17:55:00.001-05:00

Stuart B. Lowe developed a detection system capable of simultaneous evaluation of the activity of two critical enzyme classes, proteases and kinases. Peptide substrates were synthesized by LifeTein. http://bit.ly/pAxoWm

2011-12-13T17:08:00.001-05:00

LifeTein is filling in over the holidays http://ping.fm/HIKdJ

2011-12-06T15:43:00.001-05:00

LifeTein helped characterize the immune response to HIV-1 using host derived epitope R7V. http://bit.ly/uHsjzm

2011-11-30T14:28:00.001-05:00

Patent Awarded to Kansas State Univ. for Synthetic Canine Antimicrobial Peptide: http://ping.fm/IHhtm

2011-11-30T14:19:00.001-05:00

Cell-penetrating peptides combat atopic Eczema in new study. http://bit.ly/ui4e07

2011-11-29T15:53:00.001-05:00

D-enantiomer of LL-37, synthesized by LifeTein, could be a treatment for P. aeruginosa infection. http://bit.ly/tfDD8U

Obesity Treatment: A New Peptide Drug

2011-11-23T14:36:00.001-05:00

Obesity Treatment: A New Peptide Drug

During the past 20 years, there has been a dramatic increase in obesity in the United States and rates remain high. In 2010, no state in the United States had a prevalence of obesity less than 20%. Approximately one in three adults and one in six children are obese. Obesity is epidemic in the United States today and a major cause of death, attributable to heart disease, cancer, and diabetes.

Despite significant efforts in the past decade, very few drugs have been successfully developed for the treatment of obese patients. 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. Orlistat (Xenical) is a weight-loss medication for long-term weight loss. This medication blocks the digestion and absorption of fat in your stomach and intestines. Other attempts to treat obesity have also predominantly focused on drugs aimed at suppressing appetite or increasing metabolism, but these efforts have been hampered by their toxic side-effects. Unfortunately, it’s common to regain weight no matter what obesity treatment methods you try.

In contrast, an MD Anderson group designed a new drug, the ligand-directed peptidomimetic CKGGRAKDC-GG-D(KLAKLAK)2 (termed adipotide), which is a synthetic peptide that triggers cell death. The drug acts on white adipose tissue. The white adipose tissue is the unhealthy type of fat that accumulates under the skin and around the abdomen.

In earlier preclinical research, obese mice lost about 30 percent of their body weight with this peptidomimetic peptide. Monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function. Overall and abdominal body fat levels drop, with reversible renal side effects Weight, BMI and abdominal circumference all continued to drop for three weeks after treatment ended before slowly beginning to reverse during the fourth week of the follow-up period. Monkeys in the studies demonstrated no signs of nausea or food avoidance. The renal effect was dose-dependent, predictable and reversible. This is a potentially important finding since unpleasant side-effects have limited the use of approved drugs that reduce fat absorption in the intestines.

Together, these data in primates establish adipotide as a prototype in a new class of candidate drugs that may be useful for treating obesity in humans.

This is an alternative approach based on libraries of natural, highly structured peptides that offers new opportunities for identifying effective, specific inhibitors of protein-protein interactions. Peptide libraries constitute virtually all of the available classes of protein fold structures, providing a rich source of peptides that interact specifically and with high affinity to human proteins.

Using peptide library, the MD Anderson group is able to screen and identify those that bind to specific vascular cells among the many possible “ZIP codes” present in a human vascular map. This approach may help not only in understanding the implications of each interaction identified within the interactome but also in the development of effective drugs targeted to particular protein functions. Although peptide libraries are active in animal models, the challenge remains to demonstrate efficacy and safety in a clinical setting.

This video explains the many factors that have contributed to the obesity epidemic, and showcases several community initiatives taking place to prevent and reduce obesity. Obesity is a national epidemic and a major contributor to some of the leading causes of death in the U.S., including heart disease, stroke, diabetes and some types of cancer. We need to change our communities into places that strongly support healthy eating and active living.

Obesity Treatment: A New Peptide Drug

2011-11-23T14:33:00.001-05:00

2011-11-23T10:55:00.001-05:00

A Peptidomimetic CKGGRAKDC-GG-D(KLAKLAK)2 could treat obesity: http://bit.ly/soghky.

2011-11-01T16:12:00.001-04:00

Peptide LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) may be used to fight Influenza. http://1.usa.gov/tbG5EW

2011-10-20T16:49:00.001-04:00

Srinivasan identified that RON2 (Synthesized by LifeTein), a parasite protein, could be a potential vaccine candidate. http://bit.ly/pAxoWm

2011-10-19T09:36:00.001-04:00

Xiao Z Shen from Bernstein’s lab found that the carboxypeptidase angiotensin-converting enzyme shapes the MHC class I peptide repertoire. http://ping.fm/j2Hao

Peptide vaccine research: problems and accomplishments

2011-10-07T11:12:00.001-04:00

On October 5, 2011, Apple’s Steve Jobs died in California at age 56, seven years after being diagnosed with pancreatic cancer. Pancreatic cancer, a malignant neoplasm of the pancreas, is the fourth most common cause of cancer death worldwide. Jobs’s death is a great loss for the technology industry, and it highlights the need for effective treatments for pancreatic and other cancers.

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. A number of peptide vaccines have been successfully used to produce antigen-specific responses in pancreatic cancer patients by targeting the differences between healthy and cancerous cells.

Mucin 1 (MUC1) is a type I transmembrane glycoprotein found on cancer cells. MUC1’s extracellular domain, which is composed of a polypeptide core with multiple tandem repeats of a 20 amino acid sequence with numerous carbohydrate chains. Peptide vaccines allow the body’s own HLA-unrestricted cytotoxic T lymphocytes (CTLs) to recognize cancerous cells. In one early study, a humoral immune response against MUC1 was also shown, and circulating antibodies against its tandem repeat peptides were detected in various cancers. These findings led researchers to recognize the potential applications of MUC1 in cancer immunotherapy. MUC1 peptide vaccines are currently in clinical trials.

Cancer cells also differ from healthy ones in their telomere-building enzymes and vascular endothelial growth factors (VEGF). A telomerase-based vaccine, known as GV1001 peptide, was found to induce a telomerase-specific immune response in 63% of evaluable patients, as measured by DTH in nonresectable pancreatic cancer. Another peptide epitope vaccine, VEGF receptor (VEGFR)2–169, has been administered alongside gemcitabine to patients with advanced pancreatic cancer. A total of 83% of patients showed a median overall survival time of 8.7 months. Phase II and III studies of this VEGFR2–169 peptide vaccine therapy are currently under way in patients with recurrent pancreatic cancer.

Peptide vaccines can even be tailored to specific patients. In one pilot study, pancreatic and colorectal cancer patients were vaccinated with K-Ras peptides containing patient-specific mutations. Of the patients who received the vaccine, 20% were still alive. Memory T-cell responses were observed in 75% of the survivors. In addition, some effort has been made to generate peptide vaccines based on the specific tumor-antigen epitopes that are most immunogenic in a given patient.

Unfortunately, the advantages that peptide vaccines offer are somewhat diminished by their lack of inherent immunogenicity, as can be seen in their clinical results, which, while encouraging, do not equal those of other types of vaccines. However, there are several ways in which the immunogenicity of peptide vaccines can be increased. Key anchor residues within the peptides, such those that bind to MHC-I molecules, can be mutated. Target peptides can be linked to more highly immunogenic peptides or to antibodies. For example, the TAT protein from HIV, which facilitates entry into cells, has been fused to antigens in order to enhance uptake by cells.

Successful clinical application of peptide vaccines requires a strong understanding of how pancreatic cancers evade immune recognition and target immune suppressor mechanisms. Although peptide vaccines constitute an attractive path for immunotherapy, there are various issues that must be addressed in order to increase the likelihood that these vaccines will preferentially stimulate high-quality CTL responses. Close examination of peptide dosage and vaccine formulation and identification of potential cryptic T cell epitopes will be key parts of any future clinical study.

2011-10-07T11:11:00.001-04:00

Getting peptide vaccines to work: Steve Job’s pancreatic cancer. http://ping.fm/eHKhx

2011-10-06T13:45:00.001-04:00

Steve Jobs (1955-2011) changed the way each of us sees the world.

2011-09-14T17:27:00.001-04:00

D-Peptide-Based Drug Discovery Aided by Chemical Protein Synthesis. http://bit.ly/oqP4H4

2011-09-14T17:22:00.001-04:00

Peptides from structure-based designs can disrupt the fibril formation of full-length proteins, such as tau protein, that lack fully ordered native structures. http://bit.ly/rgmo1F

Peptide Synthesis Research Award Program - Activities - IYC 2011

2011-08-14T22:51:00.000-04:00

Peptide Synthesis Research Award Program - Activities - IYC 2011

2011-08-08T13:27:00.001-04:00

IDT and Ghent University scientists Used peptides from LifeTein to study ion channel function. http://bit.ly/qN4T7q

2011-08-08T13:07:00.001-04:00

The year 2011 has been designated the International Year of Chemistry: http://ping.fm/s4AYh

2011-07-01T15:54:00.001-04:00

Cell penetrating peptide vectors named as “lipo-oligoarginine peptides” (LOAPs) can translocate into cell easily without adverse effect on cell viability. http://bit.ly/kRMzre