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.