ALEMBIC LABS
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distillation №76

Retatrutide — Replace the native Lys-20 γGlu-γGlu-C20 diacid lipidation with a single γGlu spacer and a C18 monoacid (oleoyl, cis-Δ9 octadecenoyl) chain on the Lys-20 ε-amine, yielding Lys-20(γGlu-oleoyl). All other residues unchanged.

REPLACE THE NATIVE LYS-20 ΓGLU-ΓGLU-C20 DIACID LIPIDATION WITH A SINGLE ΓGLU SPACER AND A C18 MONOACID (OLEOYL, CIS-Δ9 OCTADECENOYL) CHAIN ON THE LYS-20 Ε-AMINE, YIELDING LYS-20(ΓGLU-OLEOYL). ALL OTHER RESIDUES UNCHANGED.METABOLICMay 4, 2026[ DISCARDED ]
[↓ download report.pdf]
average confidence
69.7%
pTM
0.6767641305923462
ipTM
0.23291026055812836
binding Δ
—
agreement
—
target
Glucagon-like peptide 1 receptor
uniprot
P43220
01/

3D structure

// booting Mol* viewer

// powered by Mol* — drag to rotate · scroll to zoom · use the right panel for cartoon / spacefill / surface presets, measurements & export

chain A — peptide (plasma red)chain B+ — target / context (white)
02/

AI analysis

tldr

—

detailed analysis

—

03/

research data

A

known activity

// not yet provided by clinical agent

B

biohacker use

// not yet provided by clinical agent

C

mechanism class

// not yet provided by clinical agent

05/

folding metrics

// no per-residue pLDDT trace — Boltz-2 returned summary metrics only

aggregation propensity (window)

39 windows

confidence metrics

pLDDT mean
0.70
pTM
0.68
ipTM
0.23
Boltz ↔ Chai
—
cross-validated (borderline pLDDT)
06/

domain annotations

// not yet annotated by clinical / structural agents

07/

structural caption

No reliable 3D structure could be obtained for this peptide.

08/

peptide profile

These are sequence-based heuristic estimates, not wet-lab measurements. Real aggregation propensity requires TANGO/Aggrescan, real BBB permeability requires QSAR models, and real half-life requires PK studies. Treat the numbers as ranked indicators — useful for comparing variants, not for absolute claims.

aggregation propensity
heuristic
0.139
● good
Predicted likelihood of self-aggregation. Lower is better.
≤ 0.40 good · ≤ 0.80 moderate
source: Kyte-Doolittle window proxy
stability prediction
heuristic
0.56
● moderate
Composite stability score. Higher = more stable in solution.
≥ 0.70 good · ≥ 0.40 moderate
source: charge / proline / length composite
BBB penetration
heuristic
0.056
● —
Estimated blood-brain barrier permeability. Goal depends on target tissue.
≥ 0.50 high · ≥ 0.20 moderate
source: hydrophobic fraction proxy
half-life estimate
heuristic
long (>6 hours, depends on modifications)
● —
In-silico estimated plasma half-life range.
text estimate
source: length-bucket heuristic
09/

known binders

// no ChEMBL binders found for this target

11/

agent findings

3 findingslast updated: 2026-05-05 00:15:01 UTC
researcher: 1literature: 1structural: 1
☿RESEARCHER agentclaude-opus-4-7
2026-05-04 23:59:07 UTC· 21.3s● COMPLETED
Replace the native Lys-20 γGlu-γGlu-C20 diacid lipidation with a single γGlu spacer and a C18 monoacid (oleoyl, cis-Δ9 octadecenoyl) chain on the Lys-20 ε-amine, yielding Lys-20(γGlu-oleoyl). All other residues unchanged.
🜍LITERATURE agentclaude-sonnet-4-6
2026-05-04 23:59:28 UTC· 1m 19s● COMPLETED
11 PubMed + 4 preprints synthesised
🜔STRUCTURAL agentclaude-opus-4-7
2026-05-05 00:00:47 UTC· 14m 13s● COMPLETED
Both structure predictors failed to produce usable output for this peptide. Marking as failed.
12/

caveats

  • ─in silico prediction only — requires wet lab validation
  • ─single-run prediction (not ensembled)
  • ─predicted properties may not reflect biological reality
  • ─this is research, not medical advice
  • ─modified peptides have not been synthesized or tested
13/

data

[↓ download fold.json][↓ download structure.pdb][⊘ on-chain unavailable][⎘ copy permalink]
14/

works cited

  1. [1]

    (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial

    · PubMed PMID ↗

  2. [2]

    (2025). Retatrutide-A Game Changer in Obesity Pharmacotherapy

    · PubMed PMID ↗

  3. [3]

    (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial

    · PubMed PMID ↗

  4. [4]

    (2024). The power of three: Retatrutide's role in modern obesity and diabetes therapy

    · PubMed PMID ↗

  5. [5]

    (2024). Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials

    · PubMed PMID ↗

  6. [6]

    (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial

    · PubMed PMID ↗

  7. [7]

    (2026). Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials

    · PubMed PMID ↗

  8. [8]

    (2025). Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2 trial

    · PubMed PMID ↗

  9. [9]

    (2025). Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes: A Systematic Review of Randomized Controlled Trials

    · PubMed PMID ↗

  10. [10]

    (2024). Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss: an updated systematic review and network meta-analysis

    · PubMed PMID ↗

  11. [11]

    (2025). The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines

    · PubMed PMID ↗

  12. [12]

    (2025). Efficacy and safety of retatrutide for overweight/obesity or type 2 diabetes: a systematic review and meta-analysis

    · PubMed PMID ↗

  13. [13]

    (2026). Evaluation of Research Grade Peptides Marketed Directly to Consumers Reveals Extensive Variability in Purity and Measured Abundance

    · PubMed PMID ↗

  14. [14]

    (2025). Differential effects of glucagon-like peptide-1 receptor agonist classes on blood pressure: a systematic review and network meta-analysis

    · PubMed PMID ↗