fix(docs): correct SEED-009 Met omission + track PRs #105/#106

docs/DISCOVERY_PREDICTION.md

@@ -803,6 +803,17 @@ No biological activity has been demonstrated. The lab is the judge.*
 
 ---
 
+**Tracking note (post-PR #106):** WET_LAB_HANDOFF.md: factual correction — SEED-009 synthesis
+guidance previously stated "No Met, no Cys → standard Fmoc SPPS" for all 4 variants; corrected
+to note that VAR_033 (RRLPRPGYMPRP) has Met at position 9 (same Nle substitution + HPLC purity
+requirement as SEED-007 variants). Other 3 SEED-009 variants (VAR_027/017/039) have no Met.
+
+**Tracking note (post-PR #105):** presynth_check.py: PYROGLUTAMATE_RISK flag added for N-terminal
+Q (t½ hours–days at pH 7.4, 5–50× MIC loss); E1 excluded (acid-catalysed, negligible at
+physiological pH); Nα-acetylation or Q1→K1/R1 substitution surfaced as remediation. None of the
+20 pilot candidates are affected (no Q-terminal sequences in the pilot panel), but the check
+protects future seed generation batches.
+
 **Tracking note (post-PR #103):** ASSAY_PREREGISTRATION.md: serum stability model limitations
 block extended to cover all 5 affected families — SEED-003 (pre-existing, 11 AA length edge),
 SEED-007 (added: Met/Nle substitution + 11 AA length edge), SEED-008 (pre-existing, Trp steric,

docs/ROADMAP.md

@@ -89,6 +89,8 @@ Implemented during the pre-wet-lab improvement loop (PRs #31–#54):
 - WET_LAB_HANDOFF.md completed with dedicated special notes for all 7 seed families: SEED-007 (bombolitin-II, 4 pilot slots, all NOVEL, best serum stability, Met oxidation guidance, breakthrough-candidate framing), SEED-005 (cecropin-magainin hybrid, safety/serum risk note), SEED-008 (puroindoline-a, Trp aggregation handling, aromatic-mechanism CD interpretation), SEED-009 (Bac2A proline-rich, Pro coupling guidance, RPMI-parallel assay note restated as standalone); Serum Stability section header updated to "All 7 Seeds" with SEED-006 and SEED-007 table rows added; DISCOVERY_PREDICTION.md tracking updated (PR #100)
 - presynth_check.py Met oxidation flag strengthened: Nle (norleucine) substitution explicitly recommended, inert-atmosphere storage, mandatory HPLC purity at receipt — actionable guidance now surfaces at QC report level for all SEED-007 pilot variants (PR #102)
 - ASSAY_PREREGISTRATION.md serum stability model limitations block extended to cover all 5 affected families: SEED-003 (pre-existing, 11 AA length edge), SEED-007 (added: Met/Nle substitution + 11 AA length edge), SEED-008 (pre-existing, Trp steric, 13 AA length edge), SEED-009 (pre-existing, Pro-bond protease resistance), SEED-005 (added: safety gate, hemolysis at MIC/3 mandatory, exclude if HC₅₀ < 10× MIC); all limitations pre-registered before synthesis order (PR #103)
+- presynth_check.py: PYROGLUTAMATE_RISK flag added for N-terminal Q (cyclises to pGlu at pH 7.4, t½ hours–days, 5–50× MIC loss); E1 intentionally excluded (acid-catalysed only, negligible at physiological pH); Nα-acetylation (zero extra cost) or Q1→K1/R1 substitution surfaced as remediation; 7 tests including Q+QG double-flag interaction guard (PR #105)
+- WET_LAB_HANDOFF.md: SEED-009 synthesis guidance corrected — VAR_033 (RRLPRPGYMPRP) contains Met at position 9 (Nle substitution + HPLC purity required); the "No Met, no Cys" statement now scoped to VAR_027/017/039 only (PR #106)
 
 ## v1.0 — Validated dry-lab-to-wet-lab loop
 

docs/WET_LAB_HANDOFF.md

@@ -406,9 +406,14 @@ Pro ring conformational constraint (Vanhoof *et al.* 1995, *FASEB J* 9:736–744
 Pro-rich AMPs show > 2 h stability in 50% human serum (Otvos & Cudic 2002, *Curr Pharm Design*).
 
 **Synthesis guidance:**
-- No Met, no Cys → standard Fmoc SPPS.
-- Pro-rich sequences (50% Pro in some variants): use extended coupling times or double-coupling
-  at Pro positions; pseudoproline (Ψ-Pro) dipeptides at Pro-Ser/Thr junctions if yield is low.
+- No Cys in any variant → no disulfide risk.
+- **VAR_033 (RRLPRPGYMPRP) contains Met at position 9** — same oxidation risk as SEED-007:
+  request Nle (norleucine) substitution for oxidation-resistant synthesis; mandatory HPLC purity
+  at receipt; store at −80°C under inert atmosphere. The presynth QC report for VAR_033 will
+  carry both `MET×1` and `PROLINE_RICH_INTRACELLULAR` flags simultaneously.
+- VAR_027, VAR_017, VAR_039: No Met, no Cys → standard Fmoc SPPS.
+- Pro-rich sequences (33–42% Pro): use extended coupling times or double-coupling at Pro
+  positions; pseudoproline (Ψ-Pro) dipeptides at Pro-Ser/Thr junctions if yield is low.
 - C-terminal amidation optional (Pro-rich AMPs rely less on C-terminal charge).
 
 **Assay interpretation:**