Peptides research

KISS1R: Phase 1 Wet-Lab — KP-10 Reference + ncAA Leads C1-01, C1-02

C1-01 (D-Tyr¹/Arg(Me)⁹) and C1-02 (Ac/D-Tyr¹/Thr⁵/azaGly⁷/Arg(Me)⁹) are ncAA-modified kisspeptin decapeptide agonists of KISS1R (GPR54) selected from the Generation 1 computational pipeline (PRODIGY-estimated Kd 0.64 nM and ~140 pM respectively). This Phase 1 wet-lab compares both leads against the natural-AA reference KP-10 (YNWNSFGLRF-NH2) at Adaptyv (BLI + NPFFR1/NPFFR2 selectivity counter-screens), with cAMP HTRF at Ginkgo on top binders and plasma-stability LC-MS on leads.

OX2R-004: Phase 1 Wet-Lab — Reference + Stabilised Variant (S1)

OX2R-004-S1 is a stabilised ncAA variant (Ac + D-Arg4 + D-Tyr5) of OX2R-004, designed for ADHD via the orexin pathway and engineered to address the Gate 6 proteolytic-stability flag (predicted serum t1/2 15 to 55 min, cleavage sites 34 to 28). Phase 1 wet-lab tests OX2R-004-S1 against the natural-AA parent OX2R-004 and Orexin-B (native ligand) at Adaptyv (BLI + OX1R counter-screen), with cAMP HTRF at Ginkgo on top binders and plasma-stability LC-MS. Comparative output addresses both the stability and OX1R-selectivity flags from the computational pipeline.

MOTS-c/CK2 Phase 1 Wet-Lab: Native+K14Q refs + TA-162/TA-213

TA-162 (HC-stapled) and TA-213 (linear) are designed analogues of native MOTS-c, a 16-mer mitochondrial peptide that ACTIVATES CK2-alpha (Kd 1 nM SPR), a unique activator vs the all-inhibitor CK2 landscape. Both fix native MOTS-c's poor PK (proteolysis, no permeability/oral BA) while preserving the Met1/Tyr11/Arg13 pharmacophore and position-14 charge. Phase 1 compares both vs native MOTS-c (positive ref) and K14Q (negative control) by SPR binding (CK2-alpha), CK2 kinase-activation, and plasma-stability LC-MS.

Stabilized KP-10 Analogs

Rationally modified derivatives of kisspeptin-10 (KP-10), based on the native sequence YNWSFGLRF-NH2, may retain KISS1R receptor agonism while demonstrating improved metabolic stability and longer systemic exposure.

KISSPEPTIN-10

We hypothesize that if the pipeline is correctly calibrated, it will independently recover the published structural signature of KP-10 without prior knowledge of it: specifically, sequence validation should pass cleanly, and conformational sampling should converge on the canonical β-turn motif in the C-terminal region that governs KIS1R receptor binding.