Peptides As Therapeutics with Enhanced Bioactivity (original) (raw)
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Industrial-scale manufacturing of pharmaceutical-grade bioactive peptides
Biotechnology Advances, 2011
Recent studies have shown that most peptide sequences encrypted in food proteins confer bioactive properties after release by enzymatic hydrolysis. Such bioactivities, which include antithrombotic, antihypertensive, immunomodulatory and antioxidant properties, are among the traits that are of biological significance in therapeutic products. Bioactive peptides could therefore serve as potential therapeutic agents. Moreover, research has shown that peptide therapeutics are toxicologically safe, and present less side effects when compared to small molecule drugs. However, the major conventional methods i.e. the synthetic and biotechnological methods used in the production of peptide therapeutics are relatively expensive. The lack of commercially-viable processes for large-scale production of peptide therapeutics has therefore been a major hindrance to the application of peptides as therapeutic aids. This paper therefore discusses the plausibility of manufacturing pharmaceutical-grade bioactive peptides from food proteins; the challenges and some implementable strategies for overcoming those challenges.
ADVANCEMENTS IN PEPTIDE-BASED THERAPEUTICS: DESIGN, SYNTHESIS AND CLINICAL APPLICATIONS
Biochemical and Cellular Archives
Peptide-based therapeutics have emerged as a dynamic and versatile class of drugs with profound implications for modern medicine. This comprehensive review encompasses the key advancements in peptide design strategies, synthesis techniques, delivery systems, and clinical applications. Rational design approaches, including structure-activity relationship (SAR) studies and molecular modeling have revolutionized peptide design, enabling precise targeting and therapeutic optimization. Advances in peptide synthesis techniques, such as solid-phase peptide synthesis (SPPS) and native chemical ligation (NCL), have improved production efficiency and scalability. Peptide delivery systems, including nanoparticles, liposomes, polymers and cell-penetrating peptides (CPPs), offer enhanced bioavailability and targeted drug delivery. In clinical applications, peptide-based therapeutics span endocrine disorders, antimicrobial therapy, cancer treatment, immunomodulation, neurological disorders and cardiovascular diseases, demonstrating their wide-ranging impact on healthcare. Challenges in regulatory approval, immunogenicity, and toxicity are addressed, with an emphasis on personalized medicine and emerging modalities. Case studies highlight successful peptide-based drugs on the market, ongoing clinical trials, and real-world patient outcomes. In conclusion, this review underscores the potential of peptide-based therapeutics to revolutionize personalized and precision medicine, shaping the future of healthcare with tailored solutions to complex medical challenges.
Emerging trends in therapeutic peptide pharmaceuticals: Prospects and perspectives
Journal of Drug Delivery and Therapeutics, 2019
Over the last few decades, the inclusions of peptide drugs in the pharmaceutical formulation aspects are more contemporary and recurrent. Since peptide moieties for the treatment of various clinical conditions has been started worthwhile since 1930's. There has been an increasingly sustainable research work regarding the formulation of therapeutic peptides are in the arena, as probably several entities ar e already in the clinical investigation, whereas few more are in the pipeline for clinical indication. In this current discussion, it has been aimed to unleash the potential of therapeutic bioactive peptides and its future prospects, in the area of pharmaceutical formulation. A plinth of area in regard to the, demand for the development of pharmaceutical formulation of bioactive peptides are still need to be uncovered. And hence only we have discussed deeply about the contemporary prospects of the peptide moieties.
Strategic Approaches to Improvise Peptide Drugs as Next Generation Therapeutics
International Journal of Peptide Research and Therapeutics
In recent years, the occurrence of a wide variety of drug-resistant diseases has led to an increase in interest in alternate therapies. Peptide-based drugs as an alternate therapy hold researchers' attention in various therapeutic fields such as neurology, dermatology, oncology, metabolic diseases, etc. Previously, they had been overlooked by pharmaceutical companies due to certain limitations such as proteolytic degradation, poor membrane permeability, low oral bioavailability, shorter half-life, and poor target specificity. Over the last two decades, these limitations have been countered by introducing various modification strategies such as backbone and side-chain modifications, amino acid substitution, etc. which improve their functionality. This has led to a substantial interest of researchers and pharmaceutical companies, moving the next generation of these therapeutics from fundamental research to the market. Various chemical and computational approaches are aiding the production of more stable and long-lasting peptides guiding the formulation of novel and advanced therapeutic agents. However, there is not a single article that talks about various peptide design approaches i.e., in-silico and in-vitro along with their applications and strategies to improve their efficacy. In this review, we try to bring different aspects of peptide-based therapeutics under one article with a clear focus to cover the missing links in the literature. This review draws emphasis on various in-silico approaches and modification-based peptide design strategies. It also highlights the recent progress made in peptide delivery methods important for their enhanced clinical efficacy. The article would provide a bird's-eye view to researchers aiming to develop peptides with therapeutic applications.
ACS Sustainable Chemistry & Engineering, 2019
mixture (2 × 3 mL each). A solution of Fmoc-Leu-OH (3 equiv), N,N′-diisopropylcarbodiimide (DIC) (3 equiv), and Oxyma Pure (3 equiv) in the proper mixture, preactivated for 5 min, was charged onto the resin and stirred for 1 h. After the peptide coupling, the resin was washed with DMF, DCM and DMF or mixture, iPrOH, and mixture (2 × 3 mL each). Then, 20% piperidine in DMF or selected mixture was charged on the resin (2 × 3 mL × 15 min). The resin was washed and ready for the subsequent couplings, deprotections, and washings, as reported before, to obtain the pentapeptide. The peptide was cleaved from the resin with trifluoroacetic acid (TFA)/H 2 O/ triisopropylsilane (TIS) (95:2.5:2.5) solution for 2 h at room temperature. The crude was directly analyzed by HPLC-MS. Solid-Phase Synthesis of H-D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol (Linear Octreotide) in 70:30 Anisole/Dimethyl Carbonate (Method 8). The synthesis was performed in a glass syringe, attached at the bottom to a vacuum source to remove excess of reagents and solvents. The resin (H-Thr(tBu)-ol-2CT-PS 0.6 mmol/g, 500 mg) was washed with 3 mL of Mix C3, 3 mL of iPrOH, and 3 mL of Mix C3. A preactivated solution of Fmoc-Cys(Trt)-OH (3 equiv), DIC (3 equiv), and Oxyma Pure (3 equiv) in Mix C3 (3.3 mL) was charged onto the resin and stirred for 1 h. After the peptide coupling, the resin was washed with 3 mL of Mix C3, 3 mL of iPrOH, and 3 mL of Mix C3. Fmoc removal was performed by adding 2 × 3 mL of 20% piperidine in Mix C3 on the resin, shaking it for 10 min each. After the deprotection, the resin was washed with 4 × 3 mL of Mix C3. The resin was ready for the subsequent couplings, deprotections, and washings, as reported before, to obtain the decapeptide. The final washings were performed with Mix C3 (4 × 3 mL) and iPrOH (3 × 2 mL). The peptide was cleaved from the resin with TFA/TIS/1-dodecanthiol (9 mL/0.7 mL/0.6 mL) solution for 4 h at room temperature. The solution was recovered by filtration. Diisopropyl ether (37 mL) was added dropwise at 0−5°C to the acidic solution until precipitation of peptide was achieved. The resulting mixture was stirred for 1.5 h at 0−5°C. The precipitate was filtered, washed with diisopropyl ether and petroleum ether, and dried under vacuum, affording an off-white solid. The crude was analyzed by HPLC-MS. For the synthesis with method 1, as a substitution for Mix C3 and iPrOH, DMF and DCM were used. Cyclization of Linear Octreotide. Crude trifluoroacetate linear Octreotide (1 g of a raw synthetic product containing 82.3% or 88.0%
Current trends and perspectives of bioactive peptides
The remarkable growth of therapeutic peptide development in the past decade has led to a large number of market approvals and the market value is expected to hit $25 billion by 2018. This significant market increase is driven by the increasing incidences of metabolic and cardiovascular diseases and technological advancements in peptide synthesis. For this reason, the search for bioactive peptides has also increased exponentially. Many bioactive peptides from food and nonfood sources have shown positive health effects yet, obstacles such as the need to implement efficient and cost-effective strategies for industrial scale production, good manufacturing practices as well as well-designed clinical trials to provide robust evidence for supporting health claims continue to exist. Several other factors such as the possibility of allergenicity, toxicity and the stability of biological functions of the peptides during gastrointestinal digestion would need to be addressed.
Peptide therapy reinforced with nanotechnology: an innovative strategy for controlled drug delivery
Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition
Peptide systems are designed from specific markers of a certain pathology, use unique chemical signals that allow them to reduce the possibility of side effects by focusing their field of action. They also have a molecular volume small enough to be produced in large quantities, while they are as advanced than high molecular weight molecules. Despite these characteristics, they are still sensitive to metabolism, to physiological changes and may accumulate outside the target.; Together, these factors reduce the half-life of the treatment and limit its application. Therefore, biocompatible vehicles are needed that protect the therapeutic load and guarantee its delivery in the pharmacological receptor. For the production of these systems should be considered the route of administration, the half-life of the dose and the process of its biodegradation, and this is where nanomaterials can be exploited, since they would be created with the chemical versatility to resist the route and can also be functionalized in accordance with the requirements for the target.[1]
An overview on the field of micro- and nanotechnologies for synthetic Peptide-based vaccines
Journal of drug delivery, 2011
The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity.
Chemical Methods for Peptide and Protein Production
Molecules, 2013
Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported -ketoacid-hydroxylamine ligations with 5oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.