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Semantic Search: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.921
· Account tjphuhs@gmail.com
· 5/3/2026, 10:40:57 AM
A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from onthepen@substack.com on 2026-05-03T14:40:57.000Z View this post on the web at https://onthepen.substack.com/p/a-molecular-stapler-could-make-glp The body has always known something drug developers are still learning: shape matters. Not just the shape of a molecule as it enters a receptor, but the shape it holds after hours in the bloodstream, after the body has done everything it does to break thi
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.903
· Account tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z ---------- Forwarded message ---------- From: Dave Knapp from On The Pen <onthepen@substack.com> Date: May 3, 2026 at 10:41 AM -0400 To: tjphuhs@gmail.com Subject: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. > The body has always known something drug developers are still learning: shape matters. > ͏
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.903
· Account oc.tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z ---------- Forwarded message ---------- From: Dave Knapp from On The Pen <onthepen@substack.com> Date: May 3, 2026 at 10:41 AM -0400 To: tjphuhs@gmail.com Subject: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. > The body has always known something drug developers are still learning: shape matters. > ͏
A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.903
· Account tjphuhs@gmail.com
· 5/3/2026, 10:40:57 AM
A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from onthepen@substack.com on 2026-05-03T14:40:57.000Z pharmacologically active cores of each drug while leaving off the fatty acid chains used for extended release. To the tail end of each peptide, they attached a short additional sequence that PapB could recognize and staple into a ring. When they added the enzyme, it completed the ring on all three analogs, every single time, with nothing left unreac
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.903
· Account oc.tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z the drugs work. But the question researchers keep returning to is whether they can work better, last longer, and hold their shape more completely against the body’s own cleanup systems. > A team at the University of Utah thinks a bacterial enzyme that almost no one was paying attention to might be part of the answer. > The lock, the key, and what h
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.903
· Account tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z the drugs work. But the question researchers keep returning to is whether they can work better, last longer, and hold their shape more completely against the body’s own cleanup systems. > A team at the University of Utah thinks a bacterial enzyme that almost no one was paying attention to might be part of the answer. > The lock, the key, and what h
A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.902
· Account tjphuhs@gmail.com
· 5/3/2026, 10:40:57 AM
A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from onthepen@substack.com on 2026-05-03T14:40:57.000Z this research is called PapB. It comes from bacteria, and it belongs to a class of natural molecular machines that bacteria use to sculpt small protein chains into closed ring shapes, a process called macrocyclization. The way to picture it is this: instead of leaving the tail end of the key exposed and vulnerable, PapB acts as a molecular stapler t
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.895
· Account oc.tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z time, with nothing left unreacted. In laboratory terms, that is a perfect result. > That closed ring at the tail end of the peptide does several things worth understanding. It blocks the exoproteases that would otherwise begin dismantling the key from that end. It also stiffens the tail of the molecule, reducing the kind of loose molecular movement
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.895
· Account tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z time, with nothing left unreacted. In laboratory terms, that is a perfect result. > That closed ring at the tail end of the peptide does several things worth understanding. It blocks the exoproteases that would otherwise begin dismantling the key from that end. It also stiffens the tail of the molecule, reducing the kind of loose molecular movement
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.888
· Account tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z stapler that loops the tail back and snaps it into a closed ring. An exoprotease trying to attack from that end suddenly has nowhere to grab. The key holds its shape longer. It stays in the lock. > The scientific community knew PapB existed, but it was considered too finicky to be broadly useful as a drug development tool. The enzyme was believed t
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.888
· Account oc.tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z stapler that loops the tail back and snaps it into a closed ring. An exoprotease trying to attack from that end suddenly has nowhere to grab. The key holds its shape longer. It stays in the lock. > The scientific community knew PapB existed, but it was considered too finicky to be broadly useful as a drug development tool. The enzyme was believed t
A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.887
· Account tjphuhs@gmail.com
· 5/3/2026, 10:40:57 AM
A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from onthepen@substack.com on 2026-05-03T14:40:57.000Z Utah and co-founded a company called Sethera Therapeutics built around this enzyme platform. The research was funded by the National Institute of General Medical Sciences, part of the National Institutes of Health. This work is proof of concept, meaning it is a meaningful early step but not a finished drug. The GLP-1 analogs used in the experiments
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.887
· Account oc.tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z a finished drug. The GLP-1 analogs used in the experiments were stripped of their fatty acid chains, so they are not identical to the medications currently on the market. Whether PapB can be applied to the full clinical compounds, and whether the ring-shaped structures it creates show meaningfully better performance in animal studies or human trial
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.
Score 0.887
· Account tjphuhs@gmail.com
· 5/3/2026, 2:45:39 PM
Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z a finished drug. The GLP-1 analogs used in the experiments were stripped of their fatty acid chains, so they are not identical to the medications currently on the market. Whether PapB can be applied to the full clinical compounds, and whether the ring-shaped structures it creates show meaningfully better performance in animal studies or human trial
New Study Worth Knowing About: GLP-1s and Alzheimer's
Score 0.717
· Account tjphuhs@gmail.com
· 4/30/2026, 10:19:32 AM
New Study Worth Knowing About: GLP-1s and Alzheimer's from derekpruski@substack.com on 2026-04-30T14:19:32.000Z block the enzyme that creates tangles Tau gets converted into tangles by an enzyme called GSK-3β. GLP-1 drugs activate a signaling pathway (called PI3K/Akt) that inhibits GSK-3β. Less GSK-3β activity = less tau gunking up = fewer tangles forming inside neurons. 5. They help the brain clean itself out Your brain has its own waste-clearance system that flushes out toxic proteins. GLP-1 r
New Study Worth Knowing About: GLP-1s and Alzheimer's
Score 0.714
· Account tjphuhs@gmail.com
· 4/30/2026, 10:19:32 AM
New Study Worth Knowing About: GLP-1s and Alzheimer's from derekpruski@substack.com on 2026-04-30T14:19:32.000Z gets exciting: 22 out of 30 studies showed reductions in amyloid-beta plaques 19 out of 30 studies showed reductions in tau tangles That’s about 73% showing plaque reduction and 63% showing tangle reduction. In research terms, that’s a strong, consistent signal — not a one-off finding. By drug: Liraglutide — the most studied of the four. The most consistent. Reduced both plaques AND ta
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's
Score 0.707
· Account oc.tjphuhs@gmail.com
· 4/30/2026, 11:00:22 AM
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's from tjphuhs@gmail.com on 2026-04-30T15:00:22.000Z That’s about 73% showing plaque reduction and 63% showing tangle reduction. In research terms, that’s a strong, consistent signal — not a one-off finding. > By drug: > > • > Liraglutide — the most studied of the four. The most consistent. Reduced both plaques AND tangles across multiple models. > • > Dulaglutide — fewer studies, but consistent. Reduced both plaques and tangles, and impro
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's
Score 0.707
· Account tjphuhs@gmail.com
· 4/30/2026, 11:00:22 AM
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's from tjphuhs@gmail.com on 2026-04-30T15:00:22.000Z That’s about 73% showing plaque reduction and 63% showing tangle reduction. In research terms, that’s a strong, consistent signal — not a one-off finding. > By drug: > > • > Liraglutide — the most studied of the four. The most consistent. Reduced both plaques AND tangles across multiple models. > • > Dulaglutide — fewer studies, but consistent. Reduced both plaques and tangles, and impro
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's
Score 0.703
· Account tjphuhs@gmail.com
· 4/30/2026, 11:00:22 AM
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's from tjphuhs@gmail.com on 2026-04-30T15:00:22.000Z factory level. > 4. They block the enzyme that creates tangles > Tau gets converted into tangles by an enzyme called GSK-3β. GLP-1 drugs activate a signaling pathway (called PI3K/Akt) that inhibits GSK-3β. > Less GSK-3β activity = less tau gunking up = fewer tangles forming inside neurons. > 5. They help the brain clean itself out > Your brain has its own waste-clearance system that flus
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's
Score 0.703
· Account oc.tjphuhs@gmail.com
· 4/30/2026, 11:00:22 AM
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's from tjphuhs@gmail.com on 2026-04-30T15:00:22.000Z factory level. > 4. They block the enzyme that creates tangles > Tau gets converted into tangles by an enzyme called GSK-3β. GLP-1 drugs activate a signaling pathway (called PI3K/Akt) that inhibits GSK-3β. > Less GSK-3β activity = less tau gunking up = fewer tangles forming inside neurons. > 5. They help the brain clean itself out > Your brain has its own waste-clearance system that flus
GLP-1s vs. Addiction
Score 0.703
· Account tjphuhs@gmail.com
· 3/11/2026, 6:07:04 PM
GLP-1s vs. Addiction from huntershealthhacks@mail.beehiiv.com on 2026-03-11T22:07:04.000Z what it does and does not prove. The research is observational. That means it identifies associations between GLP-1 drugs and addiction outcomes. It does not prove that the drugs directly caused the reduction in addiction risk. The study population also consisted mostly of older male veterans with type 2 diabetes. That population may not perfectly represent the broader public. Researchers also cannot fully
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's
Score 0.702
· Account tjphuhs@gmail.com
· 4/30/2026, 11:00:22 AM
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's from tjphuhs@gmail.com on 2026-04-30T15:00:22.000Z development is full of compounds that worked beautifully in mice and failed in humans. Mouse models are typically genetically engineered to develop pathology fast — which doesn’t fully mirror what happens in a human brain over decades. > 2. The lead author’s framing is the right one — prevention, not treatment. The researchers explicitly say these drugs may work as a preventative, not as
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's
Score 0.702
· Account oc.tjphuhs@gmail.com
· 4/30/2026, 11:00:22 AM
Fwd: New Study Worth Knowing About: GLP-1s and Alzheimer's from tjphuhs@gmail.com on 2026-04-30T15:00:22.000Z development is full of compounds that worked beautifully in mice and failed in humans. Mouse models are typically genetically engineered to develop pathology fast — which doesn’t fully mirror what happens in a human brain over decades. > 2. The lead author’s framing is the right one — prevention, not treatment. The researchers explicitly say these drugs may work as a preventative, not as
New Study Worth Knowing About: GLP-1s and Alzheimer's
Score 0.695
· Account tjphuhs@gmail.com
· 4/30/2026, 10:19:32 AM
New Study Worth Knowing About: GLP-1s and Alzheimer's from derekpruski@substack.com on 2026-04-30T14:19:32.000Z the right one — prevention, not treatment. The researchers explicitly say these drugs may work as a preventative, not as a treatment for people who already have established cognitive impairment. That tracks with the human trial data — those trials enrolled people who already had Alzheimer’s. By that point, you may simply be too late. 3. The multi-mechanism story is genuinely promising.
Fwd: How Long Does It Actually Take To Resensitize Your GLP-1 Receptors?
Score 0.691
· Account oc.tjphuhs@gmail.com
· 3/15/2026, 2:45:56 PM
Fwd: How Long Does It Actually Take To Resensitize Your GLP-1 Receptors? from tjphuhs@gmail.com on 2026-03-15T18:45:56.000Z > Upgrade to paid > First, Why Do Receptors Desensitize In The First Place? > GLP-1 receptors aren’t just in your stomach - they’re distributed throughout your gut, brain, and nervous system. When a long-acting GLP-1 compound is being administered week after week, those receptors are receiving a continuous, sustained signal. Over time the body does what it always does - it