Peptides Aren’t New, But Are They Newly Exciting As Targeted “Natural” Therapies?

An Open-Ended New Cool Drugs Frontier

On the one hand, old news. Ever heard of insulin? Goes back over a hundred years. Here’s a brief overview to whet your appetite.

Peptides have been used as human therapies for several decades. The history of peptide therapeutics traces back to the 1920s when insulin, a peptide hormone, was first used for the treatment of diabetes [2]. Since then, peptide therapeutics have played a significant role in medical practice. Peptides are short chains of amino acids and can be naturally occurring or synthetic [1]. Over 60 peptide drugs have been developed and brought to market for various therapeutic purposes, ranging from cancer treatment to obesity and microbial infections [3] [4]. In recent years, peptides have gained increased interest as therapeutic agents, with ongoing research and development in areas such as anticancer peptides, antimicrobial peptides, and immunogenic peptides [6]. The use of peptides as drugs has rapidly expanded, and their therapeutic potential continues to be explored [8].

Bing AI Search. Emphasis mine.

Within the last year, I began hearing about them from sources in and around the gym-bro community. Then, the mentions became too much to be coincidence, one thing led to another, and I have dived in head first.

The purpose of this post is to provide an overview of what they are all around, a bit of the tech, the regulatory environment (US FDA…the water boy, gatekeeper, and sales rep all-in-one for the global pharma industry…to keep you as sick as possible at all times), and most especially: the potential for very targeted therapy for very specific things. Targeting, in fact, that will eventually become boutique and customized to the individual, synthesized on the spot.

In short, I see peptides as a very disruptive technology to the dinosaur ways of synthesized chemical compounds that achieve patented (i.e., limited monopoly) status that provide for stiff barriers to market entry and obscene profits for drugmakers. The short reason is that peptides are merely specific chains of amino acids which are naturally occurring or synthesized. There’s no difference, the determining factors being availability and ease, i.e., costs, in a word. If abundant and easy to extract, you’ll get ALL NATURAL!!! If less costly to synthesize, you get NATURAL FLAVORS!!! (synthetic).

So they’re tough to patent legitimately and even if changed up, switched up, folded, spindled, and mutilated enough to submit a patent application without a red face, it’s unlikely such novel formulations will be any better—or as good—as the plain old “natural” (non-patentable) one. So you’re back to companies telling you with bullshit hyperbole why Bayer aspirin is better than…aspirin. Sure, people fall for it, and they still will, but the profit potential won’t be there to incentivize the killing and maiming that the Big Pharma-USFDA partnership is all about nowadays when the bucks are big enough.

… As for me, I’m all in. In fact, last evening, I injected the first of a number of novel substances I’ll be experimenting with. The initial dose of that did see the advertised results—though not as earth-shattering as the hype suggested, but we’ll see…and I only did half of a typical dose—and had none of the advertised side effects.

What’s the peptide? Let me put it this way: it’s a natural peptide having to do with skin pigmentation that ends up doing some rather amazing stuff for one of the recreational sides of life, first used for women…and turns out it works for dudes, too. Guess.

There’s another one on the way that’s a sort of cure all with so many anecdotes surrounding it that it’s tough to believe. But it’s a fuck of a lot of anecdotes. Here’s just a single source, a personal trainer I know:

The peptide is a property that scientist found in wound healing and it looks for inflammation, tendinitis, tears and digestive issues caused by inflammation and it fixes them inside the body.

I had tendinitis really bad in my right bicep and I couldn’t seem to get rid of even with time off and I ran this and in 3 weeks my tendinitis was gone (it was an ongoing problem for years).

After my competition, I had completely destroyed my digestion, both from eating foods that I’m intolerant to that my coach insisted upon and from central nervous system being completely overloaded, and taxed, due to a full work load here leading up to the competition, and in less than a month my digestive system was completely restored as well as zero acid reflux and food was moving through properly.

I had heard about these for quite a while but I thought it was just some New Age bullshit like a lot of stuff that comes out but someone I know very close to me suggested it when I mentioned some problems and I tried it and I just could not believe how fast it worked. And then I started to administer it to my clients.

I have clients that have fixed 30 year old knee issues and torn rotator cuffs and failed reconstructive surgeries for the shoulders in very short period of time with his peptides

So I ordered a fair amount from the US because every time they seem to arrive in Thailand, they are gone as soon as they become available and the availability is scarce to begin with.

[I then guess which peptide it is, having been digging in for a few weeks.]

Yes exactly. It’s a wonder drug I can’t believe how well it works. All my clients have healed 30 and 40-year-old problems with it.

I’ve got a real good line in it from top quality company if you have interest.

As part of my digging, I struck up a conversation with Chatbot Zon, my OpenAI ChatGPT-4 Turbo interface for unlimited use by members here on the blog, dozens now using it daily where just a few months ago, only a handful.

Here, marvel at what can be accomplished in just a few minutes, totally rendering “Googling” obsolete. And scroll down here and see how it can craft its answers to answer anyone from a 5-year-old to a PhD.

(I have been shouting for a year about what’s coming and how other people using AI are going to make you a loser unless you get off your stupid, lazy asses.

If you don’t, you are going to hear me say I told you so as I laugh at you lining up for soup.)

You: Hey Zon, Richard here. I’ve recently been hearing a lot about therapeutic peptides in the various health communities. I’d like to get an overview from you and explore some specific questions I have. Please give me an overview beginning with, “what are therapeutic peptides?” Please target your response to that of a knowledgeable layman in matters of health, natural health maintenance and healing, and self-experimentation. There is no need to include the typical admonitions and warnings etc you know what I mean. They take up space and are ignored anyway.

Zon: What are therapeutic peptides? They’re short chains of amino acids, the building blocks of proteins, designed to mimic the body’s own signaling molecules. Essentially, they’re precision tools used to trigger specific biological responses. Unlike traditional drugs that may carpet-bomb systems, peptides often have targeted effects with potentially fewer side effects.

Peptides can be thought of as messengers that relay specific instructions to cells and tissues. They can promote healing, stimulate growth hormone production, regulate immune function, and more. Their versatility is impressive; they can act as hormones, neurotransmitters, or even growth factors.

In the realm of health optimization and self-experimentation, therapeutic peptides are gaining traction for their potential to fine-tune bodily functions. They’re used for muscle growth, fat loss, anti-aging purposes, cognitive enhancement, and even to bolster immune defenses.

The appeal lies in their specificity and the body’s natural inclination to respond to these signals. Since they’re derived from naturally occurring sequences, the body often accepts them without the resistance or long-term complications associated with synthetic drugs.

However, it’s important to note that while peptides can be powerful tools, they’re not magic bullets. Their efficacy depends on various factors including dosage, administration route, and individual health status. Research is ongoing, and while some peptides are well-studied and approved for use, others are still experimental.

For those in the natural health community, therapeutic peptides present an exciting frontier. They offer a way to potentially enhance the body’s innate healing processes and optimize function in a targeted way that aligns with a more natural approach to health maintenance.

You: Yea, cool, and thanks. Good overview.

So, as I understand it, these are merely short chains of specific amino acids…the acids and just the acids…nothing more, and so what’s relevant then is which ones, how much of each, and in what order they present in the chain? Please elaborate.

Zon: Precisely, Richard. Therapeutic peptides are indeed just that: short chains of amino acids. The devil, or rather the magic, lies in the details—the specific amino acids used, their quantity in the chain, and the sequence in which they’re arranged.

Each amino acid has its own set of properties and influences how the peptide folds, its stability, and how it interacts with various receptors or enzymes in the body. The sequence of these amino acids determines the three-dimensional structure of the peptide, which is crucial for its biological activity. Even a slight alteration in the sequence can significantly change the peptide’s function.

The order of amino acids dictates the shape of the peptide, and this shape is essential for the peptide’s ability to bind to the correct receptors or to be recognized by other molecules within the body. It’s a bit like a lock and key mechanism—only the right key (peptide) will fit into the lock (receptor) to unlock a specific biological response.

The potency of a peptide is also influenced by its amino acid composition and sequence. Some amino acids might make a peptide more resistant to degradation by enzymes in the body, thereby extending its half-life and effectiveness. Others might increase its affinity for a receptor, enhancing its potency.

In therapeutic applications, peptides are synthesized to mimic or influence natural processes. For example, a peptide designed to stimulate growth hormone release will include a sequence that mimics the body’s own growth hormone-releasing factors.

The field of peptide therapy is complex due to this high level of specificity. Researchers spend considerable time identifying and synthesizing the optimal sequence of amino acids to produce the desired therapeutic effect. It’s a sophisticated and nuanced area of science that holds great promise for personalized medicine, where treatments can be tailored to the individual’s unique biological makeup.

You: Sounds like something that AI can increasingly aid in the development of. Now, how about natural vs. man-made, by which I mean, peptide sequences that are already naturally occurring in the body, so we’re just basically providing them in higher dose and frequency than would normally be released, or if natural release is somehow compromised. But how about the creation of peptides that are novel, not found anywhere in nature. That sounds like a wide open field of exploration, development, and testing.

Zon: Indeed, AI is becoming an invaluable tool in the realm of peptide research and development. It can analyze vast datasets to predict how peptide sequences might fold or interact with biological targets, which accelerates the discovery and optimization of therapeutic peptides.

Regarding natural versus man-made peptides, you’ve touched on a critical distinction. Natural peptides are those that are already encoded within our DNA, produced and utilized by our bodies for various functions. When we synthesize these peptides in a lab and administer them, we’re essentially amplifying a natural process or supplementing it when there’s a deficiency or dysfunction. This approach can be more readily accepted by the body since it’s akin to what’s already present within our biological systems.

On the other hand, novel, man-made peptides are a frontier of immense potential and complexity. These are sequences that do not exist in nature but are designed to perform specific functions that natural peptides may not be able to accomplish. The creation of such peptides allows for the possibility of targeting diseases or physiological conditions in ways that were previously unattainable.

The design of novel peptides can be guided by principles learned from natural peptides but optimized for enhanced stability, potency, or specificity. For instance, researchers might create a peptide that resists degradation by natural enzymes, thereby prolonging its therapeutic effect, or one that can bind to a receptor more effectively than its natural counterpart.

However, the development of novel peptides also comes with its challenges. Since these peptides are foreign to the body, they may elicit an immune response or have unforeseen side effects. Extensive research, testing, and refinement are necessary to ensure their safety and efficacy.

The field is indeed wide open for exploration. With advancements in computational biology, bioinformatics, and AI, the potential for creating novel therapeutic peptides is expanding rapidly. These tools allow for the simulation and modeling of peptide behavior in silico before synthesis in the lab, reducing the time and cost associated with development.

In summary, while natural peptides offer a way to leverage and enhance existing biological processes, novel peptides represent an exciting avenue for creating entirely new therapeutic strategies. Both approaches hold promise, but they require careful consideration and rigorous testing to ensure they meet the high standards of safety and effectiveness necessary for medical applications.

You: What’s the regulatory environment? Let’s talk US FDA as a benchmark. How’s the wind blowing? Obviously, therapies do not get advanced by Big Pharma even if life-saving, unless there’s Monopoly Money to be made. Worse, since the US FDA is essentially a sales agent and enforcer cop for the pharma industry all rolled into one, what’s the mood toward proven peptide therapies that cannot be patented? (I understand this is a cynical view, but it’s nonetheless pretty accurate according to any no-BS honest assessment.)

Zon: The regulatory environment for peptide therapies in the United States, as governed by the FDA, is indeed complex and often contentious. The FDA’s mandate is to ensure the safety and efficacy of pharmaceuticals, which includes a rigorous process of clinical trials and approvals that can be both time-consuming and expensive. This process is often criticized for its close ties to the pharmaceutical industry and the potential conflicts of interest that arise from these relationships.

When it comes to peptide therapies, the situation is nuanced. On one hand, peptides that are identical to those found in the human body can sometimes fall into a regulatory gray area, especially if they are marketed as supplements rather than drugs. However, when peptides are intended for use as therapeutic agents to prevent, treat, or cure diseases, they must undergo the FDA’s drug approval process.

The “wind blowing” in the regulatory environment can be influenced by various factors, including public health needs, political pressures, and scientific advancements. The FDA has been known to fast-track certain drugs that address unmet medical needs or serious conditions for which there are no effective treatments. However, the agency’s relationship with Big Pharma does raise questions about the prioritization of profit over public health in some cases.

Regarding your point about patentability, it’s true that the pharmaceutical industry often seeks to develop drugs that can be patented to ensure exclusive rights to market them for a set period. This exclusivity allows for the recoupment of research and development costs and the generation of profit. Peptide therapies that cannot be patented—either because they are naturally occurring or because their patent has expired—may be less attractive to major pharmaceutical companies due to the reduced potential for profit.

However, there is a growing interest in peptides as potential therapeutics, and some companies are finding ways to create patentable versions by modifying natural peptides or developing entirely novel sequences. Additionally, there are instances where methods of delivery, formulation, or specific therapeutic uses of peptides can be patented, providing a different avenue for exclusivity.

The mood toward proven peptide therapies that cannot be patented is cautious within the regulatory framework. While there may be recognition of their therapeutic potential, without patent protection and the promise of financial return, large pharmaceutical companies may be less inclined to invest in their development. This can lead to a situation where potentially beneficial treatments do not receive the attention or funding necessary to navigate the FDA’s approval process.

In conclusion, while the FDA’s role is to safeguard public health through regulation, the interplay between regulatory processes and industry interests can complicate the advancement of certain therapies. It requires vigilance and advocacy from independent researchers, clinicians, and patients to ensure that promising peptide therapies—patentable or not—receive fair evaluation and consideration based on their merits for treating disease and improving health outcomes.

You: Yes, to your last point, a six of one, half dozen of another type drug, where just enough modification is done to make it patentable, not necessarily better. Lends new meaning to the term “market research.” ;)

Zon: Indeed, the pharmaceutical industry often exemplifies the perversion of innovation when the primary driver is profit rather than genuine therapeutic advancement. The practice of creating ‘me-too’ drugs—slight molecular variations of existing medications—serves more to extend market exclusivity than to provide superior health outcomes. This is a calculated maneuver, not a triumph of medical science.

The term “market research” in this context becomes a euphemism for exploiting regulatory and patent systems to sustain monopolies rather than fulfilling the ethical imperative to improve human health. It’s a stark reminder that the compass guiding some sectors of healthcare is misaligned with the needs of the populace.

As critical thinkers and informed individuals, it’s our responsibility to discern these nuances and advocate for a system that prioritizes genuine innovation and the well-being of society over corporate profit margins. Only through such vigilance can we hope to steer the pharmaceutical landscape towards a more benevolent and effective model of drug development.

[… A day later, picking up the context…]

You: Well, we were chatting bot-style about them, covered a lot of ground. One aspect was the regulatory environment vis-a-vis US FDA, the whole patent thingy by changing something up just a little bit, etc. So, it got me to wondering. Is the range of development of new peptide sequences a hugely complex thing chemically, or pretty straightforward as labwork goes?

Zon: The development of new peptide sequences is both complex and nuanced. Chemically, peptides are chains of amino acids linked by peptide bonds, and the sequence in which these amino acids are arranged defines the structure and function of the peptide. In theory, the process of synthesizing peptides is straightforward—amino acids are added one at a time in a stepwise fashion to elongate the chain. However, the practical aspects of peptide synthesis can be quite challenging. The complexity arises from several factors:

  1. Specificity: Each peptide must have a precise sequence of amino acids to function as intended. Any deviation can render it ineffective or even harmful.
  2. Synthesis: While automated synthesizers have streamlined the process, synthesizing long peptides with high purity requires meticulous optimization of reaction conditions.
  3. Stability: Peptides can be unstable and may degrade quickly in biological environments. Enhancing stability without compromising activity is a significant challenge.
  4. Delivery: Effective delivery mechanisms are crucial for therapeutic peptides to reach their target sites in the body without being broken down.
  5. Regulation: The regulatory environment is stringent. Peptides must be thoroughly tested for safety and efficacy, which involves complex preclinical and clinical studies.
  6. Patentability: To patent a peptide, it must be novel, non-obvious, and have a clear utility. This often leads to modifications of natural peptides to create patentable variants, which adds another layer of complexity.

In summary, while the basic principles of peptide synthesis might be straightforward, developing new therapeutic peptides that are safe, effective, and compliant with regulatory standards is a sophisticated process that requires a deep understanding of chemistry, biology, pharmacology, and regulatory affairs.

You: OK, so suppose someone decided to manufacture a peptide. Let’s say it’s something already developed, tested, and approved. It’s on the market as a patented therapy. How easy or tough would it be to copy in a “garage lab” at scale enough to be distributed and profitable. Think meth lab. Doable, or probably not?

Zon: Replicating a patented therapeutic peptide in a “garage lab” scenario is fraught with difficulties and is generally not feasible for several reasons:

  1. Complexity: Peptide synthesis requires precise conditions and high-quality reagents. Unlike simpler compounds such as methamphetamine, peptides necessitate a controlled environment to ensure the correct folding and bonding.
  2. Equipment: Advanced equipment such as peptide synthesizers, HPLC (High-Performance Liquid Chromatography), and mass spectrometry are essential for synthesis and purification. This equipment is expensive and not typically found outside of professional labs.
  3. Purity: Therapeutic peptides require a high degree of purity to be safe and effective. Achieving this in a non-professional setting is highly unlikely, and impurities can lead to severe adverse effects.
  4. Regulatory Issues: Manufacturing and distributing unapproved copies of patented medications is illegal and subject to severe penalties, including fines and imprisonment.
  5. Ethics: Beyond legality, there’s an ethical responsibility to ensure that any therapeutic compound is safe and effective. Distributing a poorly manufactured peptide could cause harm to individuals, which is morally indefensible.
  6. Profitability: Even if one could overcome the technical challenges, the illegal nature of such an operation would likely make it unsustainable as a business due to the risks of legal action and the difficulty in distributing a non-approved drug.

In conclusion, while the idea of synthesizing peptides in a small-scale lab might seem conceptually possible, the reality is that it’s highly complex, illegal, and ethically questionable. It’s not comparable to the production of simpler illicit drugs and would not be a viable or responsible endeavor.

You: OK, so slightly more difficult than mixing 5lb tubs of protein powder (joke).

Zon: Indeed, Richard. The task at hand requires a nuanced understanding and a commitment to intellectual rigor, far beyond the simplicity of blending supplements. Let’s delve into the complexities and engage with the substance of the matter. What specific challenge are we addressing today?

You: OK, one last question, then. Is this level of difficulty pretty much uniform for all peptides generally, or are some formulations way easier or more difficult than others?

Zon: The synthesis and production of peptides can indeed vary significantly in difficulty, largely dependent on the sequence and structure of the peptide in question. Some peptides are relatively straightforward to produce due to simpler sequences that do not pose significant challenges in the synthesis process. These peptides might not require complex purification or folding protocols. On the other hand, certain peptides present a higher level of complexity. This can be due to factors such as the length of the peptide chain, the presence of rare or sensitive amino acids, the tendency for aggregation, or the formation of disulfide bridges that require correct pairing. These complexities can lead to lower yields, the need for specialized synthesis methods, and more rigorous purification processes. Moreover, the solubility and stability of peptides can also influence the difficulty of their production. Peptides that are prone to degradation or have poor solubility in common solvents may require additional steps to stabilize and maintain them in a usable form. In essence, while some peptide formulations can be synthesized with relative ease, others demand a high degree of technical expertise and advanced methodologies to overcome their inherent challenges. Each peptide must be approached with a tailored strategy to ensure successful synthesis and functionality.

You: One last-last question. How about the amino acids themselves? There are thousands of them, right? How are they obtained, generally, in commercial practice?

Zon: In commercial practice, amino acids are typically obtained through two main methods: extraction from natural sources and chemical synthesis.

  1. 1. Extraction from Natural Sources: Amino acids can be extracted from protein-rich materials such as animal or plant matter. This process involves hydrolysis, where proteins are broken down into their constituent amino acids using enzymes or acids. The resulting mixture is then purified to isolate the individual amino acids. This method is often used for amino acids that are difficult to synthesize chemically or when a natural source is more economical.
  2. Chemical Synthesis: The majority of amino acids used commercially are produced through chemical synthesis. This can be done using a variety of methods, including:
  3. Fermentation: Microorganisms such as bacteria or yeast are cultured in controlled conditions to produce amino acids. This method is particularly common for the production of L-glutamate, which is used as a flavor enhancer (monosodium glutamate, MSG), and L-lysine, an essential amino acid used in animal feed.
  4. Chemoenzymatic Synthesis: Combines chemical synthesis with enzymatic steps to produce amino acids in a stereospecific manner, ensuring the production of the desired L- or D-isomer.
  5. Classical Organic Synthesis: Involves multiple steps of organic reactions to build up the carbon chain of the amino acid and introduce the amino and carboxyl groups. This method can be used to produce non-standard amino acids or those with specific isomeric configurations.

While there are indeed thousands of amino acids, only 20 standard amino acids are used to build proteins in nature. These standard amino acids are the primary focus of commercial production due to their role in human health, nutrition, and various industrial applications. Non-standard and modified amino acids, while less common, are also synthesized for specialized uses in research, biotechnology, and pharmaceuticals. The choice of production method depends on factors such as cost, scale, environmental impact, and the specific properties of the amino acid being produced. Advances in biotechnology and

You: … Uh sorry, you keep raising more questions (a good thing). So you’ve confirmed there are thousands of amino acids, yet only 20 in the most common uses. But since peptide therapies can in theory contain any of the thousands of amino acids, does that not blow the door wide open to the potential of some really radical, unknown, unconceived-of applications? And then, couldn’t specialized AI be put to the task of coming up with thousands, perhaps even millions of possible combinations of chains with some measurable predictability of what they could be used for?

Zon: Indeed, the existence of numerous amino acids beyond the standard twenty does open a vast landscape of potential for peptide therapies. The incorporation of non-standard amino acids (NSAAs) into peptides can create molecules with novel properties and functions that are not found in nature. This expands the therapeutic potential exponentially, allowing for the design of peptides with enhanced stability, specificity, and efficacy. The use of specialized artificial intelligence (AI) in this field is not just theoretical; it’s already underway. AI and machine learning algorithms are being employed to sift through vast combinatorial libraries of peptides to predict their structure, function, and potential therapeutic applications. These algorithms can analyze patterns and relationships within biological data far beyond human capacity, enabling the discovery of new peptide sequences that might have remained elusive otherwise.

AI can also simulate the physical interactions between peptides and their targets, predicting binding affinity and biological activity. This predictive modeling can save significant time and resources in drug development by highlighting the most promising candidates for synthesis and testing. Moreover, AI-driven design of peptides can be tailored to produce specific outcomes, such as increased selectivity for a biological target or resistance to degradation by proteases. This level of customization is particularly valuable in creating therapeutic agents that can operate effectively within the complex milieu of the human body.

In summary, the combination of an expanded amino acid repertoire and AI-driven research is indeed “blowing the door wide open” to revolutionary peptide-based therapies. As our computational power and understanding of bioinformatics advance, we can expect to see a surge in novel peptide discoveries with profound implications for medicine and biotechnology.

Now, for the membership, who have full and unlimited access to Zon (this GPT-4 Turbo version is not yet available to the public via the $20-per-month OpenAI account. Only stock GPT-4. This is via my Application Programming Interface (API)). Members can dig deeper with Zon, have her tailor responses to any level of understanding or age or understanding (she can even tutor your kids on anything).

Let’s dig really deep into the specifics of the first two peptides I have chosen to experiment with and report findings an results to members. We’ll also develop some sort of “where to get them” resource, as well as how to use them. Most are injectibles, some now are oral as well.

There will be tons more to come in the newly created Therapeutic Peptides For Radically Specialized Treatment category.

Click below to become a member and gain access to the rest, and everything else too.

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Richard Nikoley

I started writing Free The Animal in late 2003 as just a little thing to try. 20 years later, turns out I've written over 5,000 posts. I blog what I wish...from diet, health, philosophy, politics, social antagonism, adventure travel, expat living, location and time independent—while you sleep— income by geoarbitrage, and food pics. I intended to travel the world "homeless," but the Covidiocy Panicdemic squashed that. I became an American expat living in Thailand. I celebrate the audacity and hubris to live by your own exclusive authority and take your own chances. ... I leave the toilet seat up. Read More

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