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‘Encrypted’ peptides could be wellspring of natural antibiotics

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Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#31

Earlier quoted context omitted.

How long did it take you to see results after taking them?

Pretty much right away for both. I think it's because with my condition; eating seems to be incredibly inflammatory. So, whenever I eat anything, I my blood pressure spikes tremendously, heart rate jumps ~15 points, I get brain fog & all kinds of other symptoms, which last several hours only to subside when I start to get really hungry again. Of course.. at that point I'm hungry, and it becomes increasingly hard to n…

I'm curious: do you have noticed any connection between what you eat (macro and micro) and the symptoms level? Because what you're describing could match dysbiosis and/or leaky gut, and you seem to have already dug really well into your condition.

Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#32

Earlier quoted context omitted.

How long did it take you to see results after taking them?

Pretty much right away for both. I think it's because with my condition; eating seems to be incredibly inflammatory. So, whenever I eat anything, I my blood pressure spikes tremendously, heart rate jumps ~15 points, I get brain fog & all kinds of other symptoms, which last several hours only to subside when I start to get really hungry again. Of course.. at that point I'm hungry, and it becomes increasingly hard to n…

Holy crap you pretty much just described me exactly. My stomach problems are minor but everything else you described is me to a tee. Interestingly the doctor has sent me to get tested for various stomach inflammatory diseases for completely different reasons, but they all came up negative.

Just googling now it seems there is no real test for IBS. How did you know that was the cause? Also, I've taken peptides before for different reasons, which ones helped you with your stomach?

Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#33
post #9
post #7

Earlier quoted context omitted.

I would have imagined labs these days just synthesise the mRNA and then let a ribosome do it’s work?

You can't always do that. Suppose you want a peptide with an unnatural amino acid... Or a natural amino acid with a specific post translational modification...

Unnatural amino acids can be done though - there's been a bunch of work on getting/finding ribosomes which will polymerize all sorts of whacky stuff.

Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#34
post #27

Another interesting Peptide. There is evidence of BPC 157 can help heal IBS, etc. 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/ Another study on its benefits regarding blood vessels. https://pubmed.ncbi.nlm.nih.gov/23782145/ An article from Ben Greenfield https://bengreenfieldfitness.com/article/supplements…

Did you find also studies on long term effects? I couldn’t find any

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.

Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#35
post #33
post #9

Earlier quoted context omitted.

You can't always do that. Suppose you want a peptide with an unnatural amino acid... Or a natural amino acid with a specific post translational modification...

Unnatural amino acids can be done though - there's been a bunch of work on getting/finding ribosomes which will polymerize all sorts of whacky stuff.

I'm aware, I used to work next to Floyd Romesberg. Yields are low, suppose you want to put TWO strange things in. Suppose you want to build a depsipeptide (or a dipeptide analog with C=C linkage). Suppose you need a 12-mer (ribosomes are very bad at short peptides).

Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#36

Earlier quoted context omitted.

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…

Does BPC-157 have to be injected? (I thought peptides were fragile and need to be refrigerated typically)

You can take it orally for gut problems.

Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#37
post #33

Earlier quoted context omitted.

Unnatural amino acids can be done though - there's been a bunch of work on getting/finding ribosomes which will polymerize all sorts of whacky stuff.

I'm aware, I used to work next to Floyd Romesberg. Yields are low, suppose you want to put TWO strange things in. Suppose you want to build a depsipeptide (or a dipeptide analog with C=C linkage). Suppose you need a 12-mer (ribosomes are very bad at short peptides).

Not saying it's easy but ribosomal synthesis of consecutive non-canonical amino acids has been achieved by some groups (https://www.cell.com/cell-chemical-biology/fulltext/S2451-94..., https://pubs.acs.org/doi/10.1021/jacs.8b07247), and many of these peptides are extremely short. Figure 5 of this manuscript describes successful applications of this for hit identification often in the context of massive peptide library screens, https://pubs.acs.org/doi/10.1021/acs.accounts.1c00391

Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#38
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.

Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#39

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 wou…

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.

Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics

#40
post #37

Earlier quoted context omitted.

I'm aware, I used to work next to Floyd Romesberg. Yields are low, suppose you want to put TWO strange things in. Suppose you want to build a depsipeptide (or a dipeptide analog with C=C linkage). Suppose you need a 12-mer (ribosomes are very bad at short peptides).

Not saying it's easy but ribosomal synthesis of consecutive non-canonical amino acids has been achieved by some groups ( https://www.cell.com/cell-chemical-biology/fulltext/S2451-94... , https://pubs.acs.org/doi/10.1021/jacs.8b07247 ), and many of these peptides are extremely short. Figure 5 of this manuscript describes successful applications of this for hit identification often in the context of massive peptide lib…

it's not really a generalizable solution, though, because suppose you need an unnatural AA that needs a specialized ribosomal cavity and that cavity hasn't been developed yet. And you need the material by a year's time. You are not going to evolve a ribosome to make your peptide. And, there are post-translational modifications that are too big to fit into ANY cavity, though in theory you could use tricksy chemistry to figure out a downstream processing step, that chemistry may not exist yet, or it may require a pure enzyme that is a pain in the ass to obtain, etc. etc. Finally, charging the correct tRNA is not necessarily easy or efficient.

Unlike well-designed programming architectures, biology is usually not "trivially composable". Oddly, SPPS is. Yes, there are corner cases, but those are more the exception than the rule.

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