Advances In Peptides Research Articles

Basics and Recent Advances in Peptide and Protein Drug Delivery

While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Despite the fact oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to make easier oral peptide delivery. As well, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonisation and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site-specific delivery are also discussed.

Peptide-based Self-assembly: Design, Bioactive Properties, and Its Applications.

The self-assembly of peptides is very popular in biomedical fields. Peptide-based assemblies have been used as an ideal candidate for drug/gene delivery, tissue engineering, and antibacterial/anticancer agents. The morphology and structure of peptide self-assembly can be changed by altering the molecular structure and the self-assembly conditions. Engineering peptide assemblies present great potential in medical fields. In this review, the structure and function of peptide self-assembly have been described. Also, the advances in peptide- based self-assembly have been highlighted in biomedical applications, such as drug packaging and delivery, tissue engineering, antibacterial agents, siRNA-targeted delivery and vaccines. Moreover, the challenges and future perspectives of the self-assembly of polypeptides are discussed.

Advances in peptides encoded by non-coding RNAs: A cargo in exosome.

The metastasis of malignant tumors determines patient prognosis. This is the main reason for the poor prognosis of patients with cancer and the most challenging aspect of treating malignant tumors. Therefore, it is important to identify early tumor markers and molecules that can predict patient prognosis. However, there are currently no molecular markers with good clinical accuracy and specificity. Many non-coding RNA (ncRNAs)have been identified, which can regulate the process of tumor development at multiple levels. Interestingly, some ncRNAs are translated to produce functional peptides. Exosomes act as signal carriers, are encapsulated in nucleic acids and proteins, and play a messenger role in cell-to-cell communication. Recent studies have identified exosome peptides with potential diagnostic roles. This review aims to provide a theoretical basis for ncRNA-encoded peptides or proteins transported by exosomes and ultimately to provide ideas for further development of new diagnostic and prognostic cancer markers.

What do we have that is new in antifungal peptides? A patent review.

Drugs used to fight fungal infections may cause toxic or adverse drug interactions. For this reason, there is an increase in the development of natural, semisynthetic and synthetic antifungal peptides. This study aimed to perform a patent review to identify the advances in peptides to treat fungal infections. In a preliminary assessment, 597 patents were identified from the database. Then, duplicated patents (62) and those with titles in disagreement with the scope of this review (196) were excluded. Then, six patents were not in English or Spanish. Following the screening, 288 patents were outside the focus of this review, according to their abstract and description. The final selection covered 45 patents.

Towards a generic prototyping approach for therapeutically-relevant peptides and proteins in a cell-free translation system

Advances in peptide and protein therapeutics increased the need for rapid and cost-effective polypeptide prototyping. While in vitro translation systems are well suited for fast and multiplexed polypeptide prototyping, they suffer from misfolding, aggregation and disulfide-bond scrambling of the translated products. Here we propose that efficient folding of in vitro produced disulfide-rich peptides and proteins can be achieved if performed in an aggregation-free and thermodynamically controlled folding environment. To this end, we modify an E. coli-based in vitro translation system to allow co-translational capture of translated products by affinity matrix. This process reduces protein aggregation and enables productive oxidative folding and recycling of misfolded states under thermodynamic control. In this study we show that the developed approach is likely to be generally applicable for prototyping of a wide variety of disulfide-constrained peptides, macrocyclic peptides with non-native bonds and antibody fragments in amounts sufficient for interaction analysis and biological activity assessment.

Advances and Perspectives of Peptide and Polypeptide‐Based Materials for Biomedical Imaging

Biomedical imaging is an effective tool to reveal internal structures beneath the skin. Such tools are of great importance for disease diagnosis and treatment. Various small molecules, polymers, and micro‐ or nanomaterials have been applied as imaging agents for contrast enhancement. Peptide‐ and polypeptide‐based materials have been designed and developed for enhanced and multifunctional imaging, due to their excellent biocompatibility and diverse biofunctionality. This review aims to summarize recent advances in peptide‐ and polypeptide‐based materials for X‐ray computed tomography (CT), magnetic resonance imaging (MRI), fluorescence imaging (FLI), positron emission tomography (PET), single‐photon emission computed tomography (SPECT), and multimodal imaging. In addition to biomedical imaging, peptide‐ and polypeptide‐based materials have also been endowed with therapeutic functions for disease theranostics. This review is concluded with a perspective on future peptide‐ and polypeptide‐based materials for biomedical imaging.

Stapling peptides using cysteine crosslinking

AbstractStapled peptides are an emerging class of cyclic peptide molecules with enhanced biophysical properties such as conformational and proteolytic stability, cellular uptake and elevated binding affinity and specificity for their biological targets. Among the limited number of chemistries available for their synthesis, the cysteine‐based stapling strategy has received considerable development in the last few years driven by facile access from cysteine‐functionalized peptide precursors. Here we present some recent advances in peptide and protein stapling where the side‐chains of cysteine residues are covalently connected with a range of different crosslinkers affording bisthioether macrocyclic peptides of varying topology and biophysical properties. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 843–852, 2016.

Recent advances in peptides for enhancing transdermal macromolecular drug delivery.

Transdermal delivery of drugs, a compelling route of systemic drug delivery, provides painless, reliable, targeted, efficient and cost effective therapeutic regimen for patients. However, its use is limited by skin barrier especially the stratum corneum barrier. Moreover, transdermal delivery of macromolecules remains a challenge. Naturally, varieties of physical methods, chemical enhancers and drug carriers have been used to counteract this limitation. Recently, transdermal peptides discovered as safer, more efficient and more specific enhancers could promote the delivery of macromolecules across the skin. Herein, the underlying transdermal peptides are included. Subsequently, we have discussed typical applications and the possible mechanism of two groups of biologically inspired transdermal peptide enhancers, namely cell penetration peptides and transdermal enhanced peptides.

Editorial (Thematic Issue: Advances in Peptides as Therapeutic Drugs)

Editorial (Thematic Issue: Advances in Peptides as Therapeutic Drugs)

ChemInform Abstract: Self‐Assembly of Peptides to Nanostructures

AbstractReview: 65 refs.

Editorial (Thematic Issue: Current Advances in Peptides for Cancer Diagnosis and Therapy)

Editorial (Thematic Issue: Current Advances in Peptides for Cancer Diagnosis and Therapy)

Protein chemical synthesis in drug discovery.

The discovery of novel therapeutics to combat human disease has traditionally been among the most important goals of research chemists. After a century of innovation, state-of-the-art chemical protein synthesis is now capable of efficiently assembling proteins of up to several hundred residues in length from individual amino acids. By virtue of its unique ability to incorporate non-native structural elements, chemical protein synthesis has been seminal in the recent development of several novel drug discovery technologies. In this chapter, we review the key advances in peptide and protein chemistry which have enabled our current synthetic capabilities. We also discuss the synthesis of D-proteins and their applications in mirror image phage-display and racemic protein crystallography, the synthesis of enzymes for structure-based drug discovery, and the direct synthesis of homogenous protein pharmaceuticals.

Basics and recent advances in peptide and protein drug delivery.

While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Although oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract. Therefore, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to facilitate oral peptide delivery. Additionally, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonization and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site-specific delivery are also discussed.

Application of Small Molecules/Macromolecules in Ocular Inflammatory Diseases

Macrobiomolecular treatments for ocular inflammatory diseases have been described in a previous review. This article mainly discusses the application of small molecules in uveitis therapy, which includes corticosteroids, salicylic acid (aspirin), metabolite analogs, and anti-oxidative agents. Additionally, we update recent advances in peptide and nucleic acid related therapies, and focus mainly on the calcineurin inhibitor, cyclosporine, oral tolerant retinal proteins/peptides, gene therapy and ribonucleic acid interference strategies. We classify these immunomodulatory agents by their molecular signatures and highlight the molecular structure and mechanisms of function. These developments in understanding molecular mechanisms of the diseases, with the advent of new technologies, advance current therapeutic approaches. The future direction is to tailor treatments to individual patients in order to provide the safest and most effective therapies for ocular inflammatory diseases.

IsoQuant: A Software Tool for Stable Isotope Labeling by Amino Acids in Cell Culture-Based Mass Spectrometry Quantitation

Accurate protein identification and quantitation are critical when interpreting the biological relevance of large-scale shotgun proteomics data sets. Although significant technical advances in peptide and protein identification have been made, accurate quantitation of high-throughput data sets remains a key challenge in mass spectrometry data analysis and is a labor intensive process for many proteomics laboratories. Here, we report a new SILAC-based proteomics quantitation software tool, named IsoQuant, which is used to process high mass accuracy mass spectrometry data. IsoQuant offers a convenient quantitation framework to calculate peptide/protein relative abundance ratios. At the same time, it also includes a visualization platform that permits users to validate the quality of SILAC peptide and protein ratios. The program is written in the C# programming language under the Microsoft .NET framework version 4.0 and has been tested to be compatible with both 32-bit and 64-bit Windows 7. It is freely available to noncommercial users at http://www.proteomeumb.org/MZw.html .

Current advances in peptide and small molecule microarray technologies

Microarrays offer a compact solution for massively parallel screening. In recent years, microarrays have branched away from the exclusive pursuit of small molecule 'hits' in target centric screens, towards the sophisticated dissection of disease biology and comparative profiling of cellular states. This has led to innovative and instructive ways in which the platform may be deployed, providing new-found methods with which to harness the throughput achievable. Library design and diversity continues to drive success with peptide and small molecule microarrays. Newer synthesis and immobilization strategies extend the already wide repertoire of fabrication methods available. Herein we describe the latest advances in the small molecule and peptide microarray arena, which herald even more exciting breakthroughs in the coming decade.

Recent Advances in Liposome‐Based Nanoparticles for Antigen Delivery

Over the last several years, new generation vaccine systems that are based on proteins, peptides, or DNA have shown great promise compared to the traditional vaccines based on inactivated or attenuated whole organisms. However, due to the lower efficiencies and higher cost of these new generation vaccines, they are seldom used alone. Rather, their formulations often contain adjuvants, either to enhance the immune responses or to reduce the effective dose. The present article will provide a brief overview of recent advances in peptide‐ or protein-based cancer vaccine adjuvants, focusing mainly on Liposome‐Protamine‐DNA (LPD) nanoparticle‐mediated antigen delivery. The molecular basis and signaling pathways leading to the activation and maturation of antigen presenting cells (APC) by adjuvants are discussed. Another consideration of the liposome‐based vaccine delivery system is the antigen targeting. Therefore, the second part of this review will discuss the strategies used for targeted delivery of antigen, from the organ level to the cellular, the sub‐cellular, and the molecular level.

Recent advances in peptide and peptidomimetic stereoisomer separations by capillary electromigration techniques

As the stereochemistry of peptides determines their physicochemical properties and biological activities, analytical methods able to discriminate between peptide stereoisomers are important especially with regard to pharmaceutical peptides and peptidomimetics. The present review summarizes recent developments in peptide and peptidomimetic stereoisomer separations by capillary electromigration techniques. The majority of separations were performed by CE while only few reports have been published on the subject of electrochromatography. In addition to systematic studies on the applicability of certain buffer additives and the evaluation of specific experimental conditions, there have been attempts to understand the mechanistic aspects of peptide stereoisomer separations as well as to analyze the structure of peptide-CD complexes.

Progress in the Development of Melanocortin Receptor Selective Ligands

The melanocortin pathway consists of endogenous agonists, antagonists, G-protein coupled receptors (GPCRs), and auxiliary proteins. This pathway has been identified to participate physiologically in numerous biological pathways including energy homeostasis, pigmentation, sexual function, inflammation, cardiovascular function, adrenal function, sebaceous gland lipid production, just to list a few. During this past decade, a clear link between the melanocortin-4 receptor (MC4R) and obesity, in both mice and humans via the regulation of food intake and energy homeostasis, has made this pathway the target of many academic and industrial research endeavors in attempts to develop potent and selective MC4R small molecules as anti-obesity therapeutic agents. Herein, we attempt to summarize the known proteins that constitute the melanocortin system and discuss advances in peptide and non-peptide drug discovery.