Taiy Chemical
(Hyp3)-Bradykinin
Synonym Hyp3-Bradykinin
Species Human
Protein Accession P01042
Purity ≥ 95%
Endotoxin Level < 0.1 EU per 1 μg of the protein
Biological Activity Measured by its ability to increase intracellular calcium concentration in human umbilical vein endothelial cells. The ED50 for this effect is typically 0.3-1 μg/mL.
Expression System E. coli
Fusion Tag None
Predicted Molecular Mass 1815.1 Daltons
Formulation Lyophilized from a 0.2 μm filtered solution of 20 mM Citrate, 150 mM NaCl, pH 3.5
Reconstitution It is recommended to reconstitute the lyophilized Hyp3-Bradykinin in sterile 18 MΩ-cm H2O not less than 100 μg/ml, which can then be further diluted to other aqueous solutions.
Storage & Stability Store lyophilized protein at -20°C. Aliquot the product after reconstitution to avoid repeated freezing/thawing cycles. Reconstituted protein can be stored at 4°C for a limited period of time.
FAQ
What is (Hyp3)-Bradykinin and how does it work?

(Hyp3)-Bradykinin is a synthetic derivative of the naturally occurring peptide bradykinin, which is involved in numerous physiological processes, particularly inflammation and blood pressure regulation. Bradykinin acts as a vasodilator, meaning it helps to widen blood vessels, thereby improving circulation and reducing blood pressure. It binds to the B2 receptor in the vascular endothelium, leading to the activation of an enzymatic cascade that results in the production of nitric oxide (NO) and other vasodilatory substances. By enhancing blood flow, bradykinin plays a critical role in maintaining cardiovascular health, wound healing, and the body's response to injury or infection.

The modification in (Hyp3)-Bradykinin, namely the substitution of a hydroxyproline (Hyp) at position 3, enhances the peptide's stability against enzymatic degradation, thus prolonging its activity in the body. This structural change might also affect the affinity and selectivity for its receptor, potentially leading to varied biological effects. The extended half-life and altered pharmacodynamics make (Hyp3)-Bradykinin a subject of interest for therapeutic applications, especially in conditions where prolonged bradykinin activity is desirable.

Research into (Hyp3)-Bradykinin also explores its potential for modulating the kinin-kallikrein system (KKS), which is a critical pathway involved in cardiovascular and renal function. The pathway is also implicated in pain and inflammatory responses. By influencing this system, (Hyp3)-Bradykinin could offer therapeutic benefits in diseases characterized by chronic inflammation or hypertension. Further studies are required to fully understand its mechanisms and potential clinical applications.

In addition to its primary vasodilatory effects, (Hyp3)-Bradykinin may interact with other signaling pathways, contributing to its complex pharmacological profile. For instance, its impact on the immune response and cellular repair mechanisms could position it as a potential candidate for treating inflammatory and autoimmune disorders. Understanding these interactions is crucial for optimizing its use in clinical settings, ensuring efficacy while minimizing adverse outcomes.

Overall, (Hyp3)-Bradykinin represents a promising area of research with various potential applications. Its development reflects the broader scientific interest in peptide-based therapeutics, offering insights into managing complex diseases through targeted biochemical modulation.

Can (Hyp3)-Bradykinin be used for managing high blood pressure?

The potential use of (Hyp3)-Bradykinin in managing high blood pressure stems from its inherent vasodilatory properties, which are characteristic of the bradykinin family of peptides. In normal physiological conditions, bradykinin contributes to the modulation of vascular tone and promotes the dilation of blood vessels, which aids in reducing peripheral resistance and subsequently lowering blood pressure. The synthetic modification in (Hyp3)-Bradykinin enhances its stability and bioactivity, which may offer therapeutic advantages over natural bradykinin in managing hypertension.

Clinical interest in (Hyp3)-Bradykinin arises from the shortcomings of conventional antihypertensive medications that might not effectively control blood pressure in all patients or cause undesirable side effects. (Hyp3)-Bradykinin's unique mechanism, focusing on enhancing nitric oxide release and endothelial function, provides an alternative approach that could complement existing therapies. This is particularly valuable for patients who have resistant hypertension or struggle with medication adherence due to side effects.

Moreover, (Hyp3)-Bradykinin's influence on the kinin-kallikrein system is pivotal, as this system plays a significant role in cardiovascular regulation beyond just the blood pressure. It is involved in electrolyte balance, inflammation, and renal function. By acting on the B2 bradykinin receptor and potentially others, (Hyp3)-Bradykinin may offer a holistic benefit to cardiovascular health, indirectly promoting heart and kidney health, which are often compromised in hypertensive patients.

However, the use of (Hyp3)-Bradykinin for hypertension remains largely investigational and is contingent on further research. Experimental studies, including animal models and early human trials, are crucial to establishing safety, optimal dosing, and long-term efficacy. Particular attention is needed for possible side effects, such as excessive vasodilation or interactions with other medications, which could complicate management strategies for patients.

While the prospects of (Hyp3)-Bradykinin in hybortension treatment hold promise, especially as part of an integrated treatment regime, its introduction into clinical practice hinges on comprehensive evaluation through well-designed clinical trials. Ongoing research efforts are essential to elucidate its role, preparing the groundwork for its potential incorporation into future blood pressure management protocols.

What are potential therapeutic applications of (Hyp3)-Bradykinin besides blood pressure regulation?

Beyond its established role in modulating blood pressure, (Hyp3)-Bradykinin has the potential for diverse therapeutic applications, attributed to its ability to interact with various biological pathways. One promising area is its use in managing chronic pain, particularly inflammatory and neuropathic pain. Bradykinin is known to be a significant mediator in the inflammatory response and pain perception. By modulating the bradykinin receptors, (Hyp3)-Bradykinin could offer a novel approach to pain management, targeting the underlying biochemical pathways rather than relying solely on traditional analgesics, which often have significant side effects.

The anti-inflammatory properties of (Hyp3)-Bradykinin also earmark it for potential use in autoimmune diseases and conditions characterized by chronic inflammation, such as rheumatoid arthritis and inflammatory bowel disease. By targeting the kinin-kallikrein system, it could reduce the levels of pro-inflammatory cytokines and mitigate tissue damage, addressing the symptoms and the cause of these debilitating diseases. Further research would help determine the efficacy and safety in such applications, particularly concerning dosing regimens and long-term effects.

Interestingly, (Hyp3)-Bradykinin's influence on cellular repair and immune responses opens doors to its application in wound healing and tissue regeneration. Accelerated healing and improved outcomes in tissue repair processes can significantly enhance recovery times and reduce the incidence of complications in patients undergoing surgery or those with chronic wounds. The enhancement of local blood flow and nutrient delivery can aid in the proliferation and differentiation of cells required for effective tissue repair.

Another exciting area is its potential role in treating acute or chronic kidney diseases. The kinin-kallikrein system has vital functions in renal physiology, influencing blood flow within the kidneys and contributing to the regulation of electrolyte balance. Through its interactions with this system, (Hyp3)-Bradykinin could aid in slowing disease progression or alleviating symptoms in renal pathologies. Its use would be complementary alongside standard treatments aimed at preserving kidney function and delaying the need for dialysis.

While the therapeutic applications of (Hyp3)-Bradykinin are promising, they require rigorous validation through research and clinical trials. The compound's multifaceted interactions necessitate comprehensive studies to fully take advantage of its therapeutic potential while managing any adverse effects. Tailoring specific applications to patient needs and ensuring safe implementation will be key challenges as researchers seek to broaden the scope of (Hyp3)-Bradykinin from laboratory research to clinical treatment.

What are the safety considerations associated with (Hyp3)-Bradykinin use?

As with any therapeutic agent, the safety considerations associated with the use of (Hyp3)-Bradykinin are paramount to its successful development and clinical application. A primary concern revolves around its potent vasodilatory effects, which, while beneficial for reducing blood pressure, could potentially lead to hypotension if not appropriately managed. This necessitates careful titration of dosage and close monitoring of patients to avoid adverse outcomes such as dizziness, fainting, or more severe cardiovascular events.

Another potential safety issue is the risk of interactions with other medications. Patients often use multiple drugs, and (Hyp3)-Bradykinin's impact on the kinin-kallikrein system may alter the metabolism or efficacy of concurrent medications, particularly those affecting cardiovascular or renal function. Comprehensive pharmacokinetic studies are required to map these interactions, ensuring that (Hyp3)-Bradykinin can be safely integrated into existing therapeutic regimens without compromising the effectiveness of other treatments or causing harmful side effects.

Immunogenicity, or the potential of (Hyp3)-Bradykinin to provoke an immune response, is another crucial safety consideration. Given that its structure differs from endogenous bradykinin, the potential for the body to identify it as foreign and mount an immune response cannot be discounted. This could result in adverse reactions ranging from mild skin irritations to severe systemic responses. Extensive preclinical testing is essential to identify and mitigate such risks before advancing to human trials.

Additionally, there might be concerns regarding the long-term use of (Hyp3)-Bradykinin, particularly its effects on physiological homeostasis. Prolonged modulation of the kinin-kallikrein system could lead to compensatory mechanisms or receptor desensitization, diminishing the agent's efficacy or causing unintended physiological changes. Monitoring and managing such potential outcomes would be imperative, requiring robust longitudinal studies and post-marketing surveillance.

Furthermore, individual variability in response to (Hyp3)-Bradykinin poses a safety challenge, as genetic and environmental factors can significantly influence treatment outcomes. Personalized medicine approaches, wherein genetic screening and individualized dosing regimens are developed, could be advantageous in managing these aspects, although they introduce additional complexity to treatment protocols.

In conclusion, while (Hyp3)-Bradykinin holds significant therapeutic potential, addressing safety concerns through meticulous research and continuous monitoring is crucial. Establishing a thorough safety profile through preclinical studies, followed by rigorous clinical trials, will be essential in ensuring that the benefits of (Hyp3)-Bradykinin outweigh any potential risks, ultimately leading to its safe and effective use in patient care.

What are the research challenges in developing (Hyp3)-Bradykinin as a therapeutic agent?

The development of (Hyp3)-Bradykinin as a therapeutic agent entails several research challenges that must be addressed to advance from the experimental stage to clinical application. One of the foremost challenges is understanding the complex biological mechanisms through which (Hyp3)-Bradykinin exerts its effects. While its vasodilatory action is well-documented, its interactions with various pathways and receptors in the body can lead to a wide range of physiological outcomes. Thorough elucidation of these mechanisms is essential to predict and manage potential therapeutic and adverse effects.

Another significant challenge is establishing the pharmacokinetic and pharmacodynamic profiles of (Hyp3)-Bradykinin. As a synthetic peptide, its stability, absorption, distribution, metabolism, and excretion (ADME) characteristics may differ significantly from those of endogenous peptides. Optimizing the formulation to enhance its stability and bioavailability while minimizing degradation or rapid clearance is a critical area of research. Developing an effective delivery system that facilitates its intended function without eliciting unwanted reactions also requires advanced techniques and innovative approaches.

Clinical trials are paramount to translating laboratory findings into practice, yet designing these trials for (Hyp3)-Bradykinin presents its own set of challenges. Identifying suitable patient populations, determining appropriate dosing regimens, and ensuring comprehensive monitoring for adverse events are complex tasks that require careful planning. Furthermore, trials must be extensive enough to provide statistically significant data while being designed to ensure ethical considerations are maintained.

Additionally, the variability in individual responses to (Hyp3)-Bradykinin presents a challenge in standardizing treatment protocols. Genetic polymorphisms, environmental factors, and interactions with other medications can greatly influence efficacy and safety outcomes. Incorporating strategies to account for personalized responses within the clinical trial design could be beneficial, yet it adds another layer of complexity to the research process.

Regulatory challenges also accompany the development of novel therapeutic peptides like (Hyp3)-Bradykinin. Ensuring compliance with regulatory standards for safety and efficacy requires meticulous documentation and adherence to strict protocols. This often involves demonstrating clear superiority or significant benefit over existing treatments, which can be difficult given the complex nature of the mechanisms involved.

In summary, while (Hyp3)-Bradykinin holds significant promise as a therapeutic agent, overcoming the associated research challenges necessitates a multidisciplinary approach. Collaboration between molecular biologists, pharmacologists, clinicians, and regulatory experts is crucial. By addressing the intricate scientific, clinical, and regulatory issues, researchers can pave the way for (Hyp3)-Bradykinin to become a viable treatment option in managing various health conditions.
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