8 ms·

‘Encrypted’ peptides could be wellspring of natural antibiotics

79 points by sizzle 5y ago

hammock 5y ago
It is a little known fact that peptides are becoming really big in the athletes/recovery/PED space. There is a lot they can do and there are so many. However we are also learning that they can cause a lot of unintended disease, cancer, etc as well.
- radicaldreamer 5y ago
  Yikes, I know there are a lot of "healing" peptides sold online for various conditions. Very spare documentation though
  - nikkwong 5y ago
    It’s scary, but I’m taking some of these myself. I had food poisoning and was diagnosed with IBS-C a few years ago and my life has been pretty deranged since then. Couldn’t sleep more than a few hours a night, couldn’t think, went from a BMI of 22 to 18. No help from doctors, or years of different drug therapies; I’ve tried everything that medicine has to offer. Also could not get my blood pressure down to save my life even on multiple meds. Fecal matter transplants helped quite a bit but still couldn’t get BP down, get good sleep, etc. Only when I started using some peptide suggested on Reddit was I able to normalize my BP and see improvements in other areas. It’s scary and I don’t recommend it (my doc certainly doesn’t, but he doesn’t endorse any of the therapies that have improved my wellbeing); I don’t want to be a guinea pig for a peptide that has a limited amount of human data to back it up; but the alternative of not using it is just so unlivable and having it solve my BP problem alone is a gift in itself. I hope I’m not shooting my future self in the foot by using these but I don’t see any alternative option currently. It sucks to be sick when medicine still hasn’t figured things out.
    - yosito 5y ago
      I've got similar health problems, and I'd love to know more about what worked for you so I can research it.
      - The_rationalist 5y ago
        He is probably talking about BPC 157
      - nikkwong 5y ago
        Thanks; I'm sorry to hear about your health problems I know how debilitating they can be. Hope your case is not as bad as mine. I'm currently self administering FMTs which I get from someone in my local community. I have tested the stool of dozens of people (which is so expensive) and have settled on this donor who has a decent stool profile. An alternative to that may be trying to get stool from humanmicrobes.org or a more "legit" way which is through the center for digestive diseases in Australia. I don't know if FMT's are helpful for all IBS patients (the research is not there yet) but anecdotally it seems like the most desperate IBS patients end up trying it to varying efficacy. I can't recommend FMT as I'm sure everyone's pathology is different and there are more traditional therapies that may work such as low FODMAP, rifaximin, or meds that increase/decrease intestinal transit time. For me, all of those therapies are embarrassingly ineffective and I think that IBS patients should at least know that FMT therapy is a thing; since it has lead to remission for many community members which gives hope that there may finally be a treatment for the most desperate. So the FMT helps in my case as well as the BPC-157 which someone else linked in the comments. I was quite surprised when my resting heart rate and blood pressure returned to my pre-disease levels within a day or two of starting the peptides. I have probably tried 3 or 4 dozen drugs at this point (mostly doctor recommended but also some from my own research); none to any effect, so seeing quick results from this new compound was shocking. I now also have more of type 2-3 stools rather than the unescapable type 1 that has plagued me ever since the diseases' inception. So that's good. I've only been using the peptides for a month so don't know what to expect. I am hoping if I can mega dose with some FMT and keep using the peptides maybe I could get into remission. Who knows. Luckily I am able to function as an engineer again for the first time in years (the brain fog is less remarkable now) so I am hoping things will return to normal but only time will tell. I hope this information is helpful but feel free to reach out if you have questions or just would like to chat because I know how lonely and lost in translation these type of health maladies can be.
- yosito 5y ago
  > we are also learning that they can cause a lot of unintended disease, cancer, etc From what I've read, as a layman, many peptides can increase cell growth which is sometimes associated with tumor growth, but they may also have a stabilizing effect on cell growth which wouldn't cause cancer at all, and could even be beneficial. I don't think there has been any evidenevidence linking peptides with cancer though. Would be eager to know if anyone has seen such evidence.
- thriftwy 5y ago
  Peptides are actually "short bits of protein" - proteins is what makes cell work. So no wonder here, that they are really big and can do a lot.
ackbar03 5y ago
Can anyone shed light on how complicated, slow, and costly it is to synthesis these proteins in vitro?
- flobosg 5y ago
  This article might help: https://cen.acs.org/articles/89/i22/Making-Peptides-Large-Scale.html https://cen.acs.org/articles/89/i22/Making-Peptides-Large-Sc...
- dnautics 5y ago
  By hand a skilled practitioner of t-boc chemistry can couple one amino acid per hour, though t-boc (boc) is disfavored since workup involves using 100% HF. Fmoc is the more popular technique and it's more like two hours. Robots can do this too, there's no real time benefit (but a robot can do more than 10 peptide couplings a day and doesn't need a lunch break -- though I guess neither does a grad student). Chief problems include: you need super concentrated protected peptides, which are highly insoluble in just about any solvent, so your system needs to have tons of filters, plus stuff gunks up your apparatus over time anyways. Then, fmoc craps out at about 20 amino acids if you're lucky, due to exponential decay of yields (99%^20, not to mention later yields can be lower due to peptide chains curling on themselves), boc can go longer. Not to mention separating what you want away from side products gets difficult. Finally the wastefulness: boc chemistry you're throwing away atoms almost 1:1 with what you're putting in to the peptide. Fmoc is typically 3:1. The solvents you use are these nasty greasy fishy smelling solvents (dmf, nmp). And the activating agents are really expensive compounds that you will slowly become allergic to if you keep working with peptides. I personally have, though unpublished work, the first total (artificial) synthesis of ubiquitin, that I did as a grad student in my first year. Although it's 76 amino acids we synthesized it in two parts and stitched them together using a technique called "native chemical ligation", though we did something special called "folding-assisted native chemical ligation".
  - robbiep 5y ago
    I would have imagined labs these days just synthesise the mRNA and then let a ribosome do it’s work?
hourislate 5y ago
Another interesting Peptide. There is evidence of BPC 157 can help heal IBS, etc. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333585/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333585/ It has other healing properties related to ligament injuries. https://pubmed.ncbi.nlm.nih.gov/21030672/ https://pubmed.ncbi.nlm.nih.gov/21030672/ Another study on its benefits regarding blood vessels. https://pubmed.ncbi.nlm.nih.gov/23782145/ https://pubmed.ncbi.nlm.nih.gov/23782145/ An article from Ben Greenfield https://bengreenfieldfitness.com/article/supplements-articles/how-to-use-bpc-157/ https://bengreenfieldfitness.com/article/supplements-article... A source for anyone interested. https://infiniwell.com/products/bpc-157 https://infiniwell.com/products/bpc-157
- gabll 5y ago
  Did you find also studies on long term effects? I couldn’t find any
  - hourislate 5y ago
    I am under the impression there are few/none. It is a something your body makes but as you age, less and less is produced. There have been a lot of folks in athletic circles who use it regularly to heal injury. It one of those things that Big Pharma can't patent so there is no interest in producing it.
noduerme 5y ago
Uh, is there any logical reason to think that the genome of a human - or any other higher level organism - has coded for unique antibiotic combinations that, e.g. various fungi which have spent the last billion years in daily fist fights with bacteria? I'm all for trawling the DNA of any creature for magical recipes, but our DNA has to code for a lot, and immune response is only a small part of it. Seems like it would be a lot more efficient to focus on phages or fungi and study what peptides they activate in response to specific bacteria, than just throwing endless processing cycles at the human genome hoping for, uh, grant money?
- temp0826 5y ago
  I wish some money would be thrown at researching Kambo (an amazonian tree frog with a poisonous secretion used by a few indigenous tribes touted for its peptide cocktail, "the vaccine of the forest"), considering its growing use. Seems like a better place to start than some of these stabs in the dark.
- jryb 5y ago
  If we were just interested in bioprospecting for new antibiotics, sure, there's more phage genome out there than human. But there's a unique value in understanding how human antibiotic peptides work (or fail to work). Does expression of human antibiotic peptides decrease with age? Are they only expressed in certain tissues? There are important implications that we'll never uncover through non-human sequence mining. Additionally, human-derived peptides will probably have fewer side effects if used therapeutically, you never know what kind of immune response some random phage peptide will elicit.
im3w1l 5y ago
There is one thing that worries me about this. See humans and pathogens have a common interest. We don't want to be killed. And they don't want to kill us. So how can this be achieved? By using stronger defences in key parts of the body. Pathogens have no incentive to circumvent them, by respecting the boundaries they can infect and spread without killing with all of the issues that come with that. But if we take the best defences and apply them everywhere this balance could be permanently disrupted. Now whether this all applies to these peptides is an open question, but I hope they will consider risk/reward carefully.
- jryb 5y ago
  We've eradicated diseases before and nothing happened (e.g. smallpox, polio). Also, the only risk is that the bacteria gain resistance to these peptides. Which isn't even that great of a risk - if humans express these peptides, we've been trying these antibiotics for millions of years. Clearly nothing bad happened.
  - im3w1l 5y ago
    I think you are missing my point. If there is an antibiotic peptide that's only expressed in the brain, then there is no benefit for bacteria to evolve resistance to it. It would make us too sick. Afflicted people would stay home which would reduce spread. Normally diseases evolve the opposite way: to be less and less harmful. This is known as Smith's "law of declining virulence". So they may even evolve vulnerability. If you take that some peptide and and put it inside your whole body, then evolving resistance becomes a high priority. Bacteria who don't do it stop spreading. And once they have evolved resistance there is no going back. You can't send a security update with new brain specific anti-biotics.
ternaryoperator 5y ago
I checked with a close friend who's spent the last 30 years in research on new antibiotics. Regarding peptides, he says, it's well-known that they're effective, but they make poor "drugs if you define 'drug' as something that you can inject or put in your mouth, have it circulate through the body, arrive intact at the site of infection, and have an effect. They usually fall apart en route; they also often induce an allergic response when you inject them."
- BizarroLand 5y ago
  I'm no expert nor have I used any but I've read that some people snort them nasally like saline, on the r/peptides subreddit. This might be my brain making things up but I think I've also heard of people taking them ocularly, putting a few drops in their eyes. I don't know where I would have read that though.

79 points by sizzle 5y ago

It is a little known fact that peptides are becoming really big in the athletes/recovery/PED space. There is a lot they can do and there are so many. However we are also learning that they can cause a lot of unintended disease, cancer, etc as well.

radicaldreamer 5y ago
Yikes, I know there are a lot of "healing" peptides sold online for various conditions. Very spare documentation though
- nikkwong 5y ago
  It’s scary, but I’m taking some of these myself. I had food poisoning and was diagnosed with IBS-C a few years ago and my life has been pretty deranged since then. Couldn’t sleep more than a few hours a night, couldn’t think, went from a BMI of 22 to 18. No help from doctors, or years of different drug therapies; I’ve tried everything that medicine has to offer. Also could not get my blood pressure down to save my life even on multiple meds. Fecal matter transplants helped quite a bit but still couldn’t get BP down, get good sleep, etc. Only when I started using some peptide suggested on Reddit was I able to normalize my BP and see improvements in other areas. It’s scary and I don’t recommend it (my doc certainly doesn’t, but he doesn’t endorse any of the therapies that have improved my wellbeing); I don’t want to be a guinea pig for a peptide that has a limited amount of human data to back it up; but the alternative of not using it is just so unlivable and having it solve my BP problem alone is a gift in itself. I hope I’m not shooting my future self in the foot by using these but I don’t see any alternative option currently. It sucks to be sick when medicine still hasn’t figured things out.
  - yosito 5y ago
    I've got similar health problems, and I'd love to know more about what worked for you so I can research it.
    - The_rationalist 5y ago
      He is probably talking about BPC 157
    - nikkwong 5y ago
      Thanks; I'm sorry to hear about your health problems I know how debilitating they can be. Hope your case is not as bad as mine. I'm currently self administering FMTs which I get from someone in my local community. I have tested the stool of dozens of people (which is so expensive) and have settled on this donor who has a decent stool profile. An alternative to that may be trying to get stool from humanmicrobes.org or a more "legit" way which is through the center for digestive diseases in Australia. I don't know if FMT's are helpful for all IBS patients (the research is not there yet) but anecdotally it seems like the most desperate IBS patients end up trying it to varying efficacy. I can't recommend FMT as I'm sure everyone's pathology is different and there are more traditional therapies that may work such as low FODMAP, rifaximin, or meds that increase/decrease intestinal transit time. For me, all of those therapies are embarrassingly ineffective and I think that IBS patients should at least know that FMT therapy is a thing; since it has lead to remission for many community members which gives hope that there may finally be a treatment for the most desperate. So the FMT helps in my case as well as the BPC-157 which someone else linked in the comments. I was quite surprised when my resting heart rate and blood pressure returned to my pre-disease levels within a day or two of starting the peptides. I have probably tried 3 or 4 dozen drugs at this point (mostly doctor recommended but also some from my own research); none to any effect, so seeing quick results from this new compound was shocking. I now also have more of type 2-3 stools rather than the unescapable type 1 that has plagued me ever since the diseases' inception. So that's good. I've only been using the peptides for a month so don't know what to expect. I am hoping if I can mega dose with some FMT and keep using the peptides maybe I could get into remission. Who knows. Luckily I am able to function as an engineer again for the first time in years (the brain fog is less remarkable now) so I am hoping things will return to normal but only time will tell. I hope this information is helpful but feel free to reach out if you have questions or just would like to chat because I know how lonely and lost in translation these type of health maladies can be.
yosito 5y ago
> we are also learning that they can cause a lot of unintended disease, cancer, etc From what I've read, as a layman, many peptides can increase cell growth which is sometimes associated with tumor growth, but they may also have a stabilizing effect on cell growth which wouldn't cause cancer at all, and could even be beneficial. I don't think there has been any evidenevidence linking peptides with cancer though. Would be eager to know if anyone has seen such evidence.
thriftwy 5y ago
Peptides are actually "short bits of protein" - proteins is what makes cell work. So no wonder here, that they are really big and can do a lot.

ackbar03 5y ago

Can anyone shed light on how complicated, slow, and costly it is to synthesis these proteins in vitro?

flobosg 5y ago
This article might help: https://cen.acs.org/articles/89/i22/Making-Peptides-Large-Scale.html https://cen.acs.org/articles/89/i22/Making-Peptides-Large-Sc...
dnautics 5y ago
By hand a skilled practitioner of t-boc chemistry can couple one amino acid per hour, though t-boc (boc) is disfavored since workup involves using 100% HF. Fmoc is the more popular technique and it's more like two hours. Robots can do this too, there's no real time benefit (but a robot can do more than 10 peptide couplings a day and doesn't need a lunch break -- though I guess neither does a grad student). Chief problems include: you need super concentrated protected peptides, which are highly insoluble in just about any solvent, so your system needs to have tons of filters, plus stuff gunks up your apparatus over time anyways. Then, fmoc craps out at about 20 amino acids if you're lucky, due to exponential decay of yields (99%^20, not to mention later yields can be lower due to peptide chains curling on themselves), boc can go longer. Not to mention separating what you want away from side products gets difficult. Finally the wastefulness: boc chemistry you're throwing away atoms almost 1:1 with what you're putting in to the peptide. Fmoc is typically 3:1. The solvents you use are these nasty greasy fishy smelling solvents (dmf, nmp). And the activating agents are really expensive compounds that you will slowly become allergic to if you keep working with peptides. I personally have, though unpublished work, the first total (artificial) synthesis of ubiquitin, that I did as a grad student in my first year. Although it's 76 amino acids we synthesized it in two parts and stitched them together using a technique called "native chemical ligation", though we did something special called "folding-assisted native chemical ligation".
- robbiep 5y ago
  I would have imagined labs these days just synthesise the mRNA and then let a ribosome do it’s work?

hourislate 5y ago

Another interesting Peptide. There is evidence of BPC 157 can help heal IBS, etc. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333585/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333585/ It has other healing properties related to ligament injuries. https://pubmed.ncbi.nlm.nih.gov/21030672/ https://pubmed.ncbi.nlm.nih.gov/21030672/ Another study on its benefits regarding blood vessels. https://pubmed.ncbi.nlm.nih.gov/23782145/ https://pubmed.ncbi.nlm.nih.gov/23782145/ An article from Ben Greenfield https://bengreenfieldfitness.com/article/supplements-articles/how-to-use-bpc-157/ https://bengreenfieldfitness.com/article/supplements-article... A source for anyone interested. https://infiniwell.com/products/bpc-157 https://infiniwell.com/products/bpc-157

gabll 5y ago
Did you find also studies on long term effects? I couldn’t find any
- hourislate 5y ago
  I am under the impression there are few/none. It is a something your body makes but as you age, less and less is produced. There have been a lot of folks in athletic circles who use it regularly to heal injury. It one of those things that Big Pharma can't patent so there is no interest in producing it.

noduerme 5y ago

Uh, is there any logical reason to think that the genome of a human - or any other higher level organism - has coded for unique antibiotic combinations that, e.g. various fungi which have spent the last billion years in daily fist fights with bacteria? I'm all for trawling the DNA of any creature for magical recipes, but our DNA has to code for a lot, and immune response is only a small part of it. Seems like it would be a lot more efficient to focus on phages or fungi and study what peptides they activate in response to specific bacteria, than just throwing endless processing cycles at the human genome hoping for, uh, grant money?

temp0826 5y ago
I wish some money would be thrown at researching Kambo (an amazonian tree frog with a poisonous secretion used by a few indigenous tribes touted for its peptide cocktail, "the vaccine of the forest"), considering its growing use. Seems like a better place to start than some of these stabs in the dark.
jryb 5y ago
If we were just interested in bioprospecting for new antibiotics, sure, there's more phage genome out there than human. But there's a unique value in understanding how human antibiotic peptides work (or fail to work). Does expression of human antibiotic peptides decrease with age? Are they only expressed in certain tissues? There are important implications that we'll never uncover through non-human sequence mining. Additionally, human-derived peptides will probably have fewer side effects if used therapeutically, you never know what kind of immune response some random phage peptide will elicit.

im3w1l 5y ago

There is one thing that worries me about this. See humans and pathogens have a common interest. We don't want to be killed. And they don't want to kill us. So how can this be achieved? By using stronger defences in key parts of the body. Pathogens have no incentive to circumvent them, by respecting the boundaries they can infect and spread without killing with all of the issues that come with that. But if we take the best defences and apply them everywhere this balance could be permanently disrupted. Now whether this all applies to these peptides is an open question, but I hope they will consider risk/reward carefully.

jryb 5y ago
We've eradicated diseases before and nothing happened (e.g. smallpox, polio). Also, the only risk is that the bacteria gain resistance to these peptides. Which isn't even that great of a risk - if humans express these peptides, we've been trying these antibiotics for millions of years. Clearly nothing bad happened.
- im3w1l 5y ago
  I think you are missing my point. If there is an antibiotic peptide that's only expressed in the brain, then there is no benefit for bacteria to evolve resistance to it. It would make us too sick. Afflicted people would stay home which would reduce spread. Normally diseases evolve the opposite way: to be less and less harmful. This is known as Smith's "law of declining virulence". So they may even evolve vulnerability. If you take that some peptide and and put it inside your whole body, then evolving resistance becomes a high priority. Bacteria who don't do it stop spreading. And once they have evolved resistance there is no going back. You can't send a security update with new brain specific anti-biotics.

ternaryoperator 5y ago

I checked with a close friend who's spent the last 30 years in research on new antibiotics. Regarding peptides, he says, it's well-known that they're effective, but they make poor "drugs if you define 'drug' as something that you can inject or put in your mouth, have it circulate through the body, arrive intact at the site of infection, and have an effect. They usually fall apart en route; they also often induce an allergic response when you inject them."

BizarroLand 5y ago
I'm no expert nor have I used any but I've read that some people snort them nasally like saline, on the r/peptides subreddit. This might be my brain making things up but I think I've also heard of people taking them ocularly, putting a few drops in their eyes. I don't know where I would have read that though.