Design, synthesis and biological evaluation of PEGylated Xenopus glucagon-like peptide-1 derivatives as long-acting hypoglycemic agents

Xenopus‐derived glucagon‐like peptide‐1 and polyethylene‐glycosylated glucagon‐like peptide‐1 receptor agonists: long‐acting hypoglycaemic and insulinotropic activities with potential therapeutic utilities

“…The long‐term glucose‐lowering activity of 33 was evaluated by pre‐oral glucose tolerance tests (OGTT) and further verified by multiple OGTT as previously described (Han et al, ). Details are shown in the Supporting Information (Table S1, Entries 3–5).…”

“…We have recently explored a non‐traditional approach to find novel GLP‐1 receptor agonists based on Xenopus GLP‐1 (Irwin et al, ; Han et al, ). Amino acid modification of Xenopus GLP‐1 generated a new GLP‐1 derivative xGLP‐1B (Table ), which is a highly potent activator of GLP‐1 receptors and better at lowering glucose levels than hGLP‐1.…”

Insights on the Structure, Molecular Weight and Activity of an Antibacterial Protein–Polymer Hybrid

“…Protein–polymer hybrid molecules are inspiring biomaterials because they retain the functions/properties of both protein and polymeric materials . For example, upon attachment of neutral polymers, the host protein often shows enhanced stability in the biological environment . This is especially useful for protein delivery wherein the protein often experiences varied (and often harsh) biochemical environments .…”

“…[1][2][3][4][5][6] For example, upon attachmento f neutralp olymers, the host protein often shows enhanced stability in the biological environment. [7][8][9][10] This is especially useful for protein delivery wherein the protein often experiences varied (and often harsh) biochemical environments. [11][12][13][14][15] When placing a" smart" polymer close to the actives ite of ap rotein, it becomes possible to control protein functionv ia controlling the polymer function.…”

The chronic administration of two novel long‐acting Xenopus glucagon‐like peptide‐1 analogs xGLP159 and XGLP296 potently improved systemic metabolism and glycemic control in rodent models

“…ABBREVIATIONS: Aib, a-aminoisobutyric acid; AUC, area under the curve; db/db, diabetic; Dde, 1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl; DIO, diet-induced obese; EC 50 , half-maximal effective concentration; Fmoc, 9-fluorenylmethyloxycarbonyl; GLP-1, glucagon-like peptide 1; HbA1c, hemoglobin A1c; ICR, Institute of Cancer Research; INS, insulin-secreting pancreatic b cell line; IOD, integrated optical density; IPGTT, intraperitoneal glucose tolerance test; PK, pharmacokinetic; RP-HPLC, reversed phase high-performance liquid chromatography; SD, Sprague-Dawley; t 1/2 , half-life; TC, total cholesterol; TG, triglyceride; xGLP-1, Xenopus GLP-1 Both liraglutide (once daily) and semaglutide (once weekly) were successfully developed by using this strategy. Two novel Xenopus (x)GLP-1 analogs (compounds 1 and 2) were recently identified by our group (15,16). The albumin-binding moiety (gGlu-palmitic acid) of liraglutide was introduced to compounds 1 and 2, and the affording compound 3 (xenoglutide) and compound 4 showed high receptor activation potency and acute in vivo hypoglycemic activities (17).…”