h09 — Synthetic Peptide Hydrogel HTC
mech. Self-assembling peptide (SAP, ~134 aa tail91 on RADA16-WH2 scaffold) forms synthetic horizontal top connectors; engages TMEM145 GOLD zone (ipTM 0.68) + G-actin (ipTM 0.51). delivery. Ototopical ear drop + LIFU round-window permeation; PKPD window 0.13-1.32 mg; $42/ear GMP via NCL. patient-fit. Works on any STRC-null including Misha; peptide wins vs maternal E1659A at 1-10 µM in 10/12 Kd scenarios.
status
A-tier. next priority reordered per STRC h09 Phase 4i Kd Sensitivity Sweep 2026-04-23:
- Phase 2c WH2 bundling (HEK293 GFP-actin confocal) — gate #1, dominates therapeutic window
- Phase 4b AF3 submission (8 jobs built, awaiting external AF3 server) — triple-complex + σ<0.05 needed
- TMEM145 SPR/BLI — gate #2, already in operable ipSAE-narrowed band
S-tier promotion path: WH2 Kd wet-lab narrowing into PASS zone (< 50 μM) + 4b triple-complex σ<0.05 → S candidate.
Recent activity
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if (p && p.file.lists.length) dv.list(p.file.lists.slice(0, 5).map(l => l.text))
else dv.paragraph("_(no log entries)_")- h09 log
- strc
- h09
- Phase 4i Kd × Kd sensitivity sweep (5×5, KD_TMEM145 10 nM-10 μM × KD_WH2_FACTIN 1 μM-1 mM) on therapeutic window: f≥0.3 reachable on 80% of plausible grid (PASS 56% single-dose + MARGINAL 24%); FAIL 20% concentrated at WH2 Kd = 1 mM column (Tβ4 analog floor, toxic ceiling beats f=0.3). Strategic finding: WH2 Kd dominates, TMEM145 Kd is secondary. Reorders wet-lab priority → Phase 2c WH2 bundling gate #1; TMEM145 SPR/BLI → #2 (ipSAE already operable-band-placed). Verdict
A_hold_multi_dose_ok, not S-robust (70% PASS threshold). A held, Mech 4 held, Deliv 3 held. → STRC h09 Phase 4i Kd Sensitivity Sweep 2026-04-23 - Dunbrack 2025 ipSAE reassessment on Ultra-Mini × TMEM145 CIFs: GOLD pruned ipSAE 0.591 sits in known-binder-zone (NFAT-CnB 0.55 … NFAT-CnA 0.78 physiological binders) → gate 3 (STRC×TMEM145 Kd) narrowed: placeholder 100 nM now lit-band-consistent (10 nM-10 µM Calcineurin-family band) instead of “arbitrary”; absolute Kd still wet-lab-gated. Full-length ipSAE 0.014 reaffirms known TM-collapse AF3 limit. Path B (AF3-only absolute Kd calibration) closed as lit-infeasible. A held, Mech 4 held. → STRC ipSAE Cross-Complex Reassessment 2026-04-23
evidence
- STRC Synthetic Peptide Hydrogel HTC — main hypothesis
- STRC Hydrogel HTC Phase 1 Self-Assembly — Phase 1-3b: analytical pre-screen → AF3 retool → full-construct validation
- STRC Hydrogel Phase 4 Computational Campaign — 8-axis campaign: 4a-4h all complete except 4b AF3 batch
scripts
models/ (legacy pool — see STRC Computational Scripts Inventory § Hypothesis 1, h09-specific rows)
hydrogel_phase1_self_assembly.pyaf3_jobs_2026-04-23b_hydrogel_builder.pythroughaf3_jobs_2026-04-23f_hydrogel_phase4b_builder.py(4 builders)hydrogel_phase4a_cif_interface_forensics.pythroughhydrogel_phase4h_endogenous_strc_competition.py(8 scripts)hydrogel_phase4c_sequence_liabilities.py— tail91_v2 Cys→Ser variant design
log
cross
- STRC Mini-STRC Single-Vector Hypothesis — h03 is primary AAV path; h09 is independent materials path
- STRC Engineered Homodimer Avidity — h26 strengthens h03; h09 is parallel non-AAV track
Connections
[part-of]STRC Hypothesis Ranking[about]Misha