Synonym |
Deltorphin I |
Species |
Human |
Protein Accession |
P01208 |
Purity |
Greater than 95% as determined by SDS-PAGE |
Endotoxin Level |
Less than 1 EU/μg |
Biological Activity |
The ED50 for this effect is typically 0.3-1.5 μg/ml. |
Expression System |
E. coli |
Fusion Tag |
GST tag |
Predicted Molecular Mass |
3098.6 Da |
Formulation |
Lyophilized from a 0.2 μm filtered solution of 20% acetonitrile and 0.1% TFA in water |
Reconstitution |
It is recommended to reconstitute the lyophilized Deltorphin I in sterile 18MΩ-cm H2O not less
than 100µg/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 Deltorphin I and how does it function in the body?
Deltorphin I is a naturally occurring
peptide recognized for its potent analgesic properties. Derived primarily from the skin of certain
species of South American frogs, Deltorphin I functions by interacting with specific receptors in the
body known as delta-opioid receptors. These receptors are a subset of the opioid receptor family which
also includes mu and kappa receptors. The primary function of Deltorphin I is to bind to these
delta-opioid receptors with high affinity, which leads to a cascade of intracellular events that result
in the modulation of pain signaling pathways.
In practical terms, when Deltorphin I binds to the
delta-opioid receptors, it initiates a series of events at the cellular level. This involves the
inhibition of adenylate cyclase activity, which consequently results in a reduction in the concentration
of cyclic AMP (cAMP) within the cell. Lower levels of cAMP lead to a diminished neuronal excitability
and reduced transmission of pain signals across synapses. Moreover, Deltorphin I also plays a role in
modulating the release of neurotransmitters, including those related to pain perception, thereby further
contributing to its analgesic effects.
Importantly, Deltorphin I's specificity for delta-opioid
receptors is significant because it implies that it operates with reduced side effects compared to other
opioids that target mu receptors, which are commonly associated with the risk of addiction and
respiratory depression. The unique interaction of Deltorphin I with its receptors also opens avenues for
potential therapeutic applications where modulating pain without the significant side effects of
traditional opioids is desired. However, while its analgesic properties are well-noted in preclinical
studies, translating these findings into clinical scenarios requires a thorough understanding of its
pharmacokinetics, metabolism, and potential interactions with other physiological systems.
Could
you explain the potential therapeutic applications of Deltorphin I?
Deltorphin I holds considerable
promise in the field of pain management due to its potent analgesic properties. Its unique ability to
bind selectively to delta-opioid receptors presents opportunities for it to be used in scenarios where
conventional opioid analgesics might present undesirable side effects or addiction potential. The
specificity of Deltorphin I for delta receptors means it could offer an alternative mechanism for pain
relief that circumvents the pitfalls associated with opioids that heavily interact with mu receptors,
such as morphine. As a result, the exploration of Deltorphin I as a therapeutic agent could extend to
the treatment of chronic pain conditions where long-term opioid use is a concern due to tolerance and
dependency issues.
Beyond its potential role in managing pain, Deltorphin I's capacity to
modulate emotional behavior suggests therapeutic applications in treating mood disorders like depression
and anxiety. Since delta-opioid receptors are implicated in mood regulation, Deltorphin I could
potentially help in alleviating symptoms of these conditions by influencing neurotransmitter pathways
associated with mood stabilization. It may act synergistically with other neurotransmitter systems to
produce a novel approach to mood modulation, offering hope for those who may not respond well to current
treatment options.
Moreover, Deltorphin I’s neuroprotective effects are a subject of interest. It
is thought that its interaction with delta-opioid receptors might help in mitigating inflammation and
cellular stress in neurodegenerative conditions. Therefore, Deltorphin I could be researched for its
utility in conditions like Alzheimer's or Parkinson's disease, where neuroinflammation is a significant
contributor to the pathology.
The potential therapeutic applications of Deltorphin I are vast,
but transitioning from research to clinical implementation requires extensive investigation. Key aspects
such as its bioavailability, safety profile, optimal dosing regimens, and long-term effects on human
physiology need thorough examination. As the scientific community continues to explore Deltorphin I's
full potential, it remains a molecular candidate of great interest in advancing pain management and
neuropsychiatric care.
How does Deltorphin I differ from other opioid peptides in terms of
chemical structure and functionality?
Deltorphin I is a distinctive amphibian peptide, which sets it
apart from other opioid peptides both in its chemical structure and its functional properties. This
particular peptide is composed of a specific sequence of amino acids that enable it to interact with
delta-opioid receptors with remarkable specificity. The unique sequence of Deltorphin I contributes to
its exceptionally high affinity for these receptors, distinguishing it from other opioid peptides such
as endorphins, enkephalins, and dynorphins whose affinities may prioritize mu or kappa opioid receptors
instead of delta.
In terms of chemical structure, Deltorphin I is characterized by its particular
peptide backbone, which is adapted for its environmental origin. Compared to endogenous opioid peptides,
which generally have a broader receptor target range, Deltorphin I exhibits a more focused interaction
with delta receptors. This is due to its evolutionary adaptation in its native species, as it provided a
survival advantage such as predator deterrence. The precise molecular configurations of Deltorphin I's
amino acids facilitate a conformational state that aligns perfectly with the binding site of
delta-opioid receptors, enhancing its binding efficacy and selectivity.
Functionally, this
specificity translates into differences in physiological and therapeutic outcomes when compared to other
opioid peptides. Deltorphin I’s affinity for delta receptors suggests a reduced tendency to provoke the
typical side effects associated with mu-opioid receptor activation, such as euphoria and addiction,
which are common issues with traditional opioids. Instead, Deltorphin I's mode of action provides
analgesia with a potentially lowered risk for these adverse effects. Furthermore, delta-opioid receptors
are less distributed than mu and kappa receptors, which potentially limits the cardiovascular,
respiratory, and gastrointestinal complications seen with other opioids.
Nonetheless, these
functional differences require detailed exploration through clinical research. Deltorphin I could be
explored for patient populations who are either intolerant or at risk of the adverse effects of
conventional opioid therapy. As research progresses, the comparison between Deltorphin I and other
opioid peptides will clarify its potential therapeutic niche, with hopes of offering an innovative
solution in pain management and beyond.
What are the challenges associated with the use of
Deltorphin I in clinical settings?
There are several challenges associated with the use of
Deltorphin I in clinical settings that researchers and clinicians need to address to harness its
potential benefits fully. One primary concern is its stability and bioavailability in the human body. As
a peptide, Deltorphin I is prone to rapid degradation by proteases, the enzymes that break down
proteins, which can severely limit its effectiveness as an administered medication. This instability
poses a significant hurdle in ensuring that sufficient concentrations reach the target delta-opioid
receptors to exert the desired analgesic effects.
Another challenge lies in the delivery
mechanisms suitable for administering Deltorphin I. Because peptides typically do not survive the
digestive process intact, oral administration is generally ineffective. Researchers must explore
alternative routes such as subcutaneous, intravenous, or intranasal delivery, each of which has its
logistical and patient compliance issues. Developing a delivery system that circumvents the rapid
degradation and ensures efficient transport to the pain sites remains a critical focus area for
advancing Deltorphin I towards clinical application.
Toxicity and side-effect profiling also
present challenges. Although Deltorphin I shows potential for reduced addiction liability due to its
delta-opioid receptor specificity, comprehensive studies are essential to ascertain long-term safety and
side effects, particularly with chronic use. The possibility of incidental activation of other receptor
types, leading to unanticipated side effects, cannot be overlooked. Additionally, the drug's effects on
populations with varying genetic constitutions related to opioid receptor variants must be thoroughly
investigated.
Furthermore, scalability of production remains a concern for any peptide-based
therapy. The extraction and synthesis of Deltorphin I in quantities sufficient for widescale use
necessitate extensive biotechnological advances. Production must be cost-effective to make it a viable
alternative to existing analgesics.
Despite these challenges, the potential advantages offered by
Deltorphin I's unique receptor interactions continue to motivate research and development. Addressing
these challenges will require interdisciplinary collaboration to transform Deltorphin I from a promising
molecular entity in laboratory studies to a robust clinical tool in pain management and potentially
other therapeutic areas. The journey from molecular discovery to medicinal application highlights the
complexities involved in translating potent biochemical properties into safe, effective
therapies.
Can Deltorphin I contribute to addiction treatment strategies given its receptor
specificity?
Deltorphin I's unique specificity for delta-opioid receptors provides a promising
avenue for exploring addiction treatment strategies. The selective engagement of delta receptors, as
opposed to the mu opioid receptors, which are primarily associated with the rewarding and addictive
properties of classical opioids like morphine and heroin, suggests that Deltorphin I might serve as a
modulation tool for addiction pathways without inducing the same level of euphoric and addictive
responses. This characteristic makes it an intriguing candidate for the development of treatments aimed
at mitigating addiction while still offering pain relief or other therapeutic benefits.
The
potential contribution of Deltorphin I to addiction treatment strategies lies in its ability to modulate
mood and reward pathways that often become dysregulated in addiction. The differentiated mechanism of
action might allow it to reduce withdrawal symptoms and cravings by stabilizing these pathways,
providing a substitute that does not perpetuate dependency. For individuals who suffer from opioid use
disorder, Deltorphin I might offer a method to alleviate certain psychological or physiological cravings
triggered by addiction, ultimately contributing to more effective withdrawal and maintenance
therapies.
Additionally, Deltorphin I might be used to support rehabilitation from addiction by
potentially aiding in mood stabilization. Many individuals with addiction disorders also experience mood
disorders such as depression or anxiety, which can lead to a cycle of self-medication using illicit
substances. By operating within the mood pathways and potentially exerting an antidepressant effect
through delta receptor engagement, Deltorphin I might help in addressing dual-diagnosis conditions,
tackling both the addiction and associated mood disorders simultaneously.
However, it is
essential to approach this potential from a scientifically rigorous standpoint. Detailed studies are
necessary to confirm the safety and efficacy of Deltorphin I in addiction treatment scenarios.
Investigations should aim to uncover its full pharmacological profile, optimal dosing regimens, and any
interaction effects when used alongside other treatment modalities for addiction. Only through
comprehensive clinical trials can the true scope of Deltorphin I’s utility in addiction treatment
strategies be realized, potentially offering a new chapter in addiction management while mitigating the
misuse and addiction cycles that plague typical opioid therapies.
How is Deltorphin I synthesized
for research and therapeutic purposes?
The synthesis of Deltorphin I for research and therapeutic
purposes involves complex processes that aim to replicate its unique peptide structure efficiently and
effectively. Given that Deltorphin I is originally sourced from the skin secretions of amphibians,
direct extraction is not feasible for large-scale production, making synthetic pathways the primary
method of obtaining this peptide.
Typically, the synthesis of Deltorphin I is conducted through
solid-phase peptide synthesis (SPPS), a method developed to facilitate the manufacture of peptides in a
controlled laboratory environment. SPPS involves the sequential addition of amino acids to a growing
peptide chain, anchored on a solid resin. The process utilizes protected amino acid derivatives which
ensure that reactions occur strictly at the desired functional groups, minimizing side reactions and
maintaining the integrity of the peptide bonds formed.
Throughout the synthesis, meticulous
control is exercised over each step to efficiently build up the peptide chain matching Deltorphin I's
sequence. Each cycle of the process involves steps of deprotection and coupling, where protective groups
are removed from the terminal amino acid to allow the next amino acid in sequence to attach. The
sequence continues until the full peptide is assembled. Once the desired peptide length is achieved, the
peptide is cleaved from the resin, and additional purification stages such as High-Performance Liquid
Chromatography (HPLC) are employed to ensure the purity and structural accuracy of the synthesized
peptide.
Advancements in peptide synthesis technologies have enhanced the efficiency and reduced
the cost of synthesizing Deltorphin I. Innovative methods are continually being developed to improve
yield and fidelity, critical for both research purposes and prospective pharmaceutical production.
Considering the therapeutic potential of Deltorphin I, robust and scalable synthesis techniques are
crucial for future applications, ensuring that sufficient quantities can be provided for extensive
clinical testing and potential therapeutic distribution.
The integrity of the synthesized
Deltorphin I is verified through various analytical techniques, including mass spectrometry and nuclear
magnetic resonance (NMR) spectroscopy, which confirm that the correct sequence and conformational
structure are achieved. These rigorous processes ensure that what is synthesized is functionally and
structurally analogous to the naturally occurring peptide, allowing for accurate experimental results
and a faithful representation of its biological effects when used in therapeutic pursuits. As research
continues, refining these synthesis methods could foster broader accessibility to Deltorphin I,
supporting further investigations into its promising pharmacological applications.