Peak-1SG 10mg

Peak-1SG is a 31-amino acid synthetic analog of human glucagon-like peptide-1, classified as a single receptor agonist. With a molecular formula of C₁₈₇H₂₉₁N₄₅O₅₉ and a molecular weight of 4,113.58 Da, it shares 94% structural homology with the native peptide. The compound is supplied as a lyophilized powder freely soluble in aqueous buffers at physiological pH.

Three critical structural modifications distinguish this compound from the native peptide. Position 8: Alanine is substituted with alpha-aminoisobutyric acid (Aib8), creating steric hindrance that prevents dipeptidyl peptidase-4 (DPP-4) cleavage at the scissile bond between positions 8 and 9. Position 34: Lysine is replaced with arginine (Arg34), preventing undesired fatty acid acylation and ensuring site-specific conjugation. Position 26: Lysine is acylated via a linker composed of two 8-amino-3,6-dioxaoctanoic acid (OEG) spacer moieties and a gamma-glutamic acid residue, terminating in an octadecanedioic acid (C18 fatty diacid) side chain. This C18 chain enables high-affinity non-covalent binding to serum albumin.

At the molecular level, Peak-1SG binds the target receptor, a class B1 G-protein-coupled receptor (GPCR). Binding induces conformational changes that facilitate coupling to the heterotrimeric G_s protein, activating adenylyl cyclase (AC) and catalyzing conversion of ATP to cyclic adenosine monophosphate (cAMP). Elevated intracellular cAMP activates two principal downstream effectors: Protein Kinase A (PKA), which phosphorylates CREB (cAMP response element-binding protein) for nuclear gene transcription, and EPAC2 (Exchange Protein Activated by cAMP 2), which activates Rap1 GTPase signaling cascades.

The compound-bound receptor-G_s complex has been resolved by cryo-electron microscopy at 2.5 angstrom resolution (PDB: 7KI0), and the peptide-receptor extracellular domain interaction has been characterized by X-ray crystallography (PDB: 4ZGM). Three-dimensional variability analysis reveals that this compound induces distinct conformational dynamics within the receptor transmembrane domain compared to the native peptide.

Supplied as a lyophilized powder for in vitro research applications only. Not for human or veterinary use.

In Vitro Research Applications: Peak-1SG is used in receptor pharmacology studies employing HEK293 and CHO cell lines stably expressing the recombinant human target receptor. These systems enable quantitative characterization of binding parameters (K_i, K_d) and concentration-dependent signaling responses. In cAMP accumulation assays, the compound produces robust, concentration-dependent cAMP generation that can be monitored in real time using FRET-based biosensors, revealing rapid onset kinetics with sustained signaling duration.

Signaling Pathway Studies: Downstream pathway interrogation includes phosphorylation assays measuring PKA substrate activation (phospho-CREB, phospho-acetyl-CoA carboxylase) by Western blot, adenylyl cyclase activity assays using membrane preparations, and beta-arrestin recruitment assays via PathHunter or BRET platforms. The Aib8 modification and albumin-binding properties confer extended receptor residence time, enabling comparative studies of sustained versus transient receptor activation kinetics.

Molecular Characterization: Identity verification is performed via MALDI-TOF or ESI mass spectrometry (expected MW 4,113.58 Da). Purity is assessed by reversed-phase HPLC. DPP-4 degradation resistance can be quantified in vitro by incubation with recombinant DPP-4 enzyme and time-course HPLC analysis. Albumin binding affinity is measurable by surface plasmon resonance (SPR/BIAcore). Peptide secondary structure may be characterized by circular dichroism (CD) spectroscopy.