‘Encrypted’ peptides could be wellspring of natural antibiotics
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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
#2Can anyone shed light on how complicated, slow, and costly it is to synthesis these proteins in vitro?
Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics
#3Can anyone shed light on how complicated, slow, and costly it is to synthesis these proteins in vitro?
This article might help: https://cen.acs.org/articles/89/i22/Making-Peptides-Large-Sc...
Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics
#4Can anyone shed light on how complicated, slow, and costly it is to synthesis these proteins in vitro?
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I personally have, though unpublished work, the first total (artificial) synthesis of ubiquitin, that I did as a grad student in my first year.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".
Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics
#5It 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.
Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics
#6It 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.
Yikes, I know there are a lot of "healing" peptides sold online for various conditions. Very spare documentation though
Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics
#7Can anyone shed light on how complicated, slow, and costly it is to synthesis these proteins in vitro?
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 prob…
I would have imagined labs these days just synthesise the mRNA and then let a ribosome do it’s work?
Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics
#8Can anyone shed light on how complicated, slow, and costly it is to synthesis these proteins in vitro?
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 prob…
There is innovation in this space. From green chemistry initiatives to replace hazardous solvents by CROs/industry invested in large-scale production of peptides, https://www.bachem.com/news/bachem-novo-nordisk-redesign-spp..., to routine solid-phase synthesis of peptides greater than 100 amino acids in hours (https://www.science.org/doi/10.1126/science.abb2491, being commercialized here https://www.amidetech.com/)
Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics
#9Earlier quoted context omitted.
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 prob…
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...
Re: ‘Encrypted’ peptides could be wellspring of natural antibiotics
#10Earlier quoted context omitted.
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 prob…
There is innovation in this space. From green chemistry initiatives to replace hazardous solvents by CROs/industry invested in large-scale production of peptides, https://www.bachem.com/news/bachem-novo-nordisk-redesign-spp... , to routine solid-phase synthesis of peptides greater than 100 amino acids in hours ( https://www.science.org/doi/10.1126/science.abb2491 , being commercialized here https://www.amidetech.com/…
Lol at the first one, replacing nmp with DMSO/EtOAc while an improvement in toxicity, it's still expensive, toxic, and hard to remove/recycle.