Track topics on Twitter Track topics that are important to you
Peptide therapeutics have traditionally faced many challenges including low bioavailability, poor proteolytic stability and difficult cellular uptake. Conformationally constraining the backbone of a peptide into a macrocyclic ring often ameliorates these problems and allows for the development of a variety of new drugs. Such peptide-based pharmaceuticals can enhance the multi-faceted functionality of peptide side chains, permitting the peptides to bind cellular targets and receptors necessary to impart their role, while protecting them from degrading cellular influences. In the work described here, we developed three cyclic peptides, VP mimic1, VP mimic2 and OT mimic1, which mimic endocrine hormones vasopressin and oxytocin. Making notable changes to the overall structure and composition of the parent hormones, we synthesized the mimics and tested their durability against treatment with three proteases chosen for their specificity: pepsin, alpha-chymotrypsin, and pronase. Vasopressin and oxytocin contain a disulfide linkage leaving them particularly vulnerable to deactivation from the reducing environment inside the cell. Thus, we increased the complexity of our assays by adding reducing agent glutathione to each mixture. Subsequently, we discovered each of our mimics withstood protease treatment with less degradation and/or a slower rate of degradation as compared to both parent hormones and a linear control peptide.
Department of Chemistry, The College of New Jersey, P.O. Box 7718, Ewing, NJ 08628, USA.
This article was published in the following journal.
Name: Bioorganic & medicinal chemistry letters
Outbreaks of acute gastroenteritis caused by noroviruses constitute a public health concern worldwide. To date, there are no approved drugs or vaccines for the management and prophylaxis of norovirus ...
A problem for "shot-gun" proteomics is that the peptides generated in the proteolysis step overwhelm the analytical capacity of current LC-MS/MS systems. A straightforward approach to overcome this pr...
Circular bacteriocins ranging from 35 to 70 amino acids are the largest cyclic peptides produced by lactic acid bacteria to suppress growth of other bacteria. Their end-to-end cyclized backbone that e...
Synthetic methods aimed at preparing peptides cross-linked by diaminodiacids remain an important chemical challenge. These cross-links are known to play a crucial role on the activity, structural stab...
Babesiosis is a tick-borne, zoonotic disease caused by species of the intraerythrocytic protozoan Babesia. It is distributed all around the world and affects various domestic and wild animals, mainly ...
Influenza virosomes represent an innovative human-compatible antigen delivery system that has already proven its suitability for subunit vaccine design. The aim of the study was to proof t...
Subjects are healthy adult volunteers either at high risk for HIV infection or already known to be seropositive, who will donate blood for in vitro tests of T-cell function and in vitro re...
This was a phase I double blind controlled vaccine trial, evaluating safety, tolerability and immunogenicity of mixtures of N, R and C LSP derived from the P. vivax CS protein formulated i...
The purpose of this study is to determine the safety and effectiveness of administering WT1 cancer peptides. Cancer peptides are short pieces of protein that are made in a laboratory to b...
Open-label single center study. Patients will be divided in four groups of 7. Group 1: 8 melanoma-specific peptides in saline; Group 2: same mix of peptides + Montanide ISA51; Group 3: sam...
The study of the similarities and differences in the structures of homologous tissues across various species.
Comparison of outcomes, results, responses, etc for different techniques, therapeutic approaches or other inputs.
A plant genus of the family VIOLACEAE. Some species in this genus are called bouncing bet which is a common name more often used with SAPONARIA OFFICINALIS. Members contain macrocyclic peptides.
The comparative study of animal structure with regard to homologous organs or parts. (Stedman, 25th ed)
Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.
Endocrine disorders are grouped into two categories: hormone imbalance - when a gland produces too much or too little of an endocrine hormone development of lesions (such as nodules or tumors) in the endocrine system, which may or may not affect...
Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake. Diagnosis is based on clinical presentation...