Defensive publication of 1,908,879 sequence-distinct peptide compositions targeting the MT1 and MT2 melatonin receptors as allosteric peptide modulators. Every disclosed composition is novel against an 11-zone real-patent-grounded markush exclusion corpus surveyed on 2026-05-02 and is dedicated to the public domain as prior art under 35 U.S.C. §102 and analogous foreign-jurisdiction novelty provisions (EPC Article 54, UK Patents Act §6, JP Patent Act §29, CN Patent Law Article 22). The disclosure decomposes to 35,198 unique linear backbones × 90 distinct form-variant chemistries spanning seven chemistry families: lipidation (988,540 compositions, 51.8%), PEGylation (397,104, 20.8%), glycosylation (303,985, 15.9%), Fc fusion (105,606, 5.5%), prodrug variants (78,314, 4.1%), glucuronidation (35,202, 1.8%), and macrocyclization (36 compositions; small subset by count, with predicted-affinity quality competitive with the form-variant families) plus salt forms and single-residue swap variants. Each composition's identity is fixed by a unique permanent identifier (CR-D07-NNNNNNN) and a structured (sequence × form-variant × cyclization) tuple in the deposit's Tier 3 JSON-Lines manifest. The deposit additionally publishes a WIPO Standard ST.26 Sequence Listing at the unique-backbone level (35,198 entries with feature annotations for form-variant modifications) for examiner-side BLAST searchability. The deposit's three-tier disclosure architecture provides per-candidate detail at proportionate depth: 100 Tier 1 candidates ship with a 15-section per-candidate HTML dossier covering sequence, predicted structure, novelty, predicted pharmacology, readiness tier, mutation map, synthesis profile, family-level synthesis route by reference, purification and QC by reference, MT1/MT2 binding-affinity assay by reference, cAMP HTRF functional confirmation by reference, predicted PK profile with form-variant-aware extension, cost and timeline estimates, and provenance with deposit-bundle SHA-256 and OpenTimestamps Bitcoin block-header attestation. 1,000 Tier 2 candidates ship as table-form HTML stubs covering sequence, predicted Kd, scaffold variant, outside-claim flag, and pointers to the universal-protocol package. The remaining 1,907,779 Tier 3 candidates are documented in the JSON-Lines manifest plus the ST.26 deposit. The deposit's universal-protocol package comprises eight family-level synthesis protocols (base Fmoc SPPS, lipidation, PEGylation, glycosylation, Fc fusion, prodrug, glucuronidation, cyclization) and three form-variant-independent characterization protocols (MT1/MT2 radioligand-displacement binding assay with 125I-2-iodomelatonin tracer and Cheng-Prusoff IC50 to Kd correction, cAMP HTRF functional readout with allosteric-cooperativity discrimination per the Christopoulos-Kenakin allosteric ternary complex model, RP-HPLC plus ESI-MS plus AAA quality control). The package satisfies the §102 enablement element under the In re Wands factors by providing family-level synthesis protocols and form-variant-independent characterization protocols for any specific disclosed composition without per-candidate inventive choice. A readiness-quality letter (A / B / C / D) summarizes each candidate's predicted-affinity tier: A bench-ready (predicted Kd less than or equal to 50 nM at primary receptor; 612,784 candidates), B research-grade (50 less than Kd less than or equal to 100 nM; 245,914), C characterization-grade (100 less than Kd less than or equal to 500 nM; 564,190), D §102 prior-art carrier (Kd greater than 500 nM; 485,991). The letter is a pure-pharmacology readout; the deposit makes no clinical or therapeutic-efficacy claim. Predicted Kd values rest on a single research-grade anchor: an 18-residue endozepine-derived hypothesis scaffold sequence (QATVGDVNTDRPGLLDLK, approximately 100 nM apparent Kd, citing Devavry 2012). The scaffold is not a contiguous fragment of human DBI (closest 18-residue DBI window QATVGDINTERPGMLDFT is a 13/18 identity match), and the Devavry citation is not independently primary-source verified by this deposit. The single-anchor calibration produces predictions at the receptor-class-template level only. The disclosure does not assert any judgment on freedom-to-operate beyond §102 novelty against the surveyed corpus. Method-of-use and method-of-treatment claims for indications outside the eleven stated MT1/MT2 utility surfaces (allosteric modulation of MT1, allosteric modulation of MT2, modulation of circadian rhythm, modulation of sleep-wake cycle, mood and affective state, pain pathways, immune signaling, cellular proliferation and oncology research, metabolic pathways, cardiovascular function, reproductive function, neuroprotection), formulation claims, combination-therapy claims, and compositions including a disclosed peptide as a component are unaffected. Filings between the 2026-05-02 corpus snapshot date and any later assertion of prior art should be re-checked. The disclosure does not claim any in-vivo activity, clinical safety, or therapeutic efficacy. The disclosure does not include or expose Coracle Research's underlying computational methodology. Published as defensive publication under 35 U.S.C. §102. Companion research note at https://www.coracleresearch.com/research/07-melatonin-pep/. Bundle includes the OpenTimestamps Bitcoin block-header attestation of the bundle SHA-256 hash for cryptographic date proof independent of the Zenodo timestamp.
Coracle Research (Sun,) studied this question.