Journal: bioRxiv

Article Title: Intrinsically Disordered Protein Coating for Oral Delivery of Peptide Drugs

doi: 10.1101/2025.10.23.684059

Figure Lengend Snippet: a , Obese mice were acclimated to oral gavage protocols and divided into groups with consistent average weights before being dosed with either oral or subcutaneous injections. b, Mouse weight change over 5 days of ExRAC administration show significant weight loss between both the oral SynIDP-encapsulated ExCDC and the oral vehicle control, and the injected ExCDC and the oral vehicle. c, Weight of mice administered with encapsulated semaglutide, free semaglutide, or vehicle were tracked over time; n=12 for therapeutic groups and n=8 for the the vehicle control. d, Blood glucose levels were measured daily for mice with orally administered semaglutide (encapsulated or free) or vehicle. Asterisks denote statistical significance (defined by * p<.05, ** p<.01, *** p<.001, **** p<.0001) as determined by 2-way ANOVA with Tukey’s test for with multiple comparison between groups at each timepoint.

Article Snippet: ExRAC and semaglutide (TargetMol Chemicals) were suspended at 5 mg/ml in 100 mM citrate phosphate buffer at a pH between 5.2 and 7.4 and mixed 1:1 (v/v) with freshly prepared 10 mg/ml SynIDP in deionized water at room temperature for at least 2 h to form nanofibers.

Techniques: Control, Injection, Comparison

Journal: Bioconjugate Chemistry

Article Title: Effect of Lipidation on the Structure, Oligomerization, and Aggregation of Glucagon-like Peptide 1

doi: 10.1021/acs.bioconjchem.4c00484

Figure Lengend Snippet: Estimation of the α-Helical Content of Freshly Dissolved 85 μM GLP-1-Am and Its Lipidated Analogues at pH 7.5

Article Snippet: Semaglutide-Am [GLP-1-Am (20, PEG2-PEG2-γ-Glu-stear)], a C-terminally amidated semaglutide analogue, H–H (Aib)EGTFTSDVSSYLEGQAAK (PEG2-PEG2-γ-Glu-stearoyl-COOH)EFIAWLVRGRG-NH 2 ; 4113 Da, was supplied by Peptides International in the form of an acetate salt with approximately 96% purity.

Techniques: Analogues, Residue

Journal: Bioconjugate Chemistry

Article Title: Effect of Lipidation on the Structure, Oligomerization, and Aggregation of Glucagon-like Peptide 1

doi: 10.1021/acs.bioconjchem.4c00484

Figure Lengend Snippet: Summary of the Distribution and Population of Oligomers in Freshly Prepared Samples of Nonlipidated GLP-1-Am and Its Lipidated Analogues a

Article Snippet: Semaglutide-Am [GLP-1-Am (20, PEG2-PEG2-γ-Glu-stear)], a C-terminally amidated semaglutide analogue, H–H (Aib)EGTFTSDVSSYLEGQAAK (PEG2-PEG2-γ-Glu-stearoyl-COOH)EFIAWLVRGRG-NH 2 ; 4113 Da, was supplied by Peptides International in the form of an acetate salt with approximately 96% purity.

Techniques: Analogues, Size-exclusion Chromatography, Sedimentation

Journal: Bioconjugate Chemistry

Article Title: Effect of Lipidation on the Structure, Oligomerization, and Aggregation of Glucagon-like Peptide 1

doi: 10.1021/acs.bioconjchem.4c00484

Figure Lengend Snippet: Summarizes the Solubility, Oligomerization, and Aggregation Behavior of all GLP-1 Analogues Studied in This Work, and Figure S15 Presents a Pictorial Representation of the Data for Each Analogue a

Article Snippet: Semaglutide-Am [GLP-1-Am (20, PEG2-PEG2-γ-Glu-stear)], a C-terminally amidated semaglutide analogue, H–H (Aib)EGTFTSDVSSYLEGQAAK (PEG2-PEG2-γ-Glu-stearoyl-COOH)EFIAWLVRGRG-NH 2 ; 4113 Da, was supplied by Peptides International in the form of an acetate salt with approximately 96% purity.

Techniques: Solubility, Analogues

Journal: Tissue barriers

Article Title: Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases.

doi: 10.1080/21688370.2023.2292461

Figure Lengend Snippet: Figure 2. BBB pharmacokinetics within one hour of 125I/14C-IRAs and 99mTc-albumin. a) Vascular space represents brain-to-serum ratio (B/S) of 99mTc-albumin. b) Delta B/S ratios of 125I/14C-IRAs, corrected for vascular space, present in whole brain over the entire time curve. n = 18 mice per IRA. c) The linear phase of transport present in (b) is used to calculate the unidirectional influx rate, Ki, presented in Figure 3 and Table 3. Tirzepatide and DA5-CH Model 1 (ns) did not significantly differ from 0. d) Early time points for DA5-CH suggest early uptake into brain (Model 2).

Article Snippet: All but one peptide (DA5-CH) was obtained from commercial sources: albiglutide (TP1796) from TargetMol (Wellesley, MA), dulaglutide (GC31520) from GLPBIO (Montclair, CA), liraglutide (6517) from Tocris Bioscience (Minneapolis, MN), semaglutide (B0084–007194) and tirzepatide (BAT-006246) from BOC Sciences (Shirley, NY).

Techniques: Drug discovery

Journal: Tissue barriers

Article Title: Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases.

doi: 10.1080/21688370.2023.2292461

Figure Lengend Snippet: Figure 5. Percent of the iv injected dose of 125I/14C-IRAs taken up per gram of brain tissue (%Inj/g). a) Current IRA %Inj/g corrected for the initial level of vascular binding (Vr), except for DA5-CH Model 2 which uses Vr = 0; n = 1–2/time point per IRA. Tirzepatide was not included as there was no measurable transport. b) The area under the curve (AUC) (from current and previous publication.50) was calculated and presented in rank order; n = 18–22 per IRA. N/A= not applicable as %Inj/g is not calculated from those that did not have significant transport within the 1 hour. DA peptides are experimental dual IRA agonists created by Christian Hölscher.38,62 Peptides 18, 19, and 21 are dual IRAs created by Finan and Ma et al. (2013).72 as numbered in their Supplementary Fig. S1.

Article Snippet: All but one peptide (DA5-CH) was obtained from commercial sources: albiglutide (TP1796) from TargetMol (Wellesley, MA), dulaglutide (GC31520) from GLPBIO (Montclair, CA), liraglutide (6517) from Tocris Bioscience (Minneapolis, MN), semaglutide (B0084–007194) and tirzepatide (BAT-006246) from BOC Sciences (Shirley, NY).

Techniques: Injection, Binding Assay

Journal: bioRxiv

Article Title: GLP-1R Agonism Directly Improves the Pumping Capacity of Murine Collecting Lymphatic Vessels

doi: 10.64898/2025.12.26.696603

Figure Lengend Snippet: (A) Percent of Glp1r -expressing cells per cell identity; (B) Average gene expression of Glp1r in LECs from WT female and WT male mice respectively; (C) Volcano plot displaying the differentially expressed genes in LECs expressing Glp1r vs. those that did not express this gene; (D) Gene ontology analyses displaying the top molecular functions and biological processes associated with the differentially upregulated genes shown in panel C; (E) Representative image of an inguinal axillary lymphatic vessel exposed to FITC-labeled semaglutide to determine GLP-1R expression and cellular localization; (F) UMAP displaying the different LEC subtypes contained within the employed scRNAseq dataset; (G) DotPlot displaying the expression of Glp1r , as well as known markers of various LEC-subtypes (in this panel, the percent of cells expressing a given feature and the average gene expression are encoded in the size and color of dots respectively); and (H) Percent of LECs expressing Glp1r in clusters linked to collecting (collLECs), pre-collecting (precLECs), or capillary (capLECs) lymphatics (cluster numbers are indicated under the horizontal axis).

Article Snippet: The cellular localization of GLP-1Rs in collecting lymphatic vessels was assessed using semaglutide conjugated with FITC (Cat. No.: HY-114118F, MedChemExpress).

Techniques: Expressing, Gene Expression, Labeling

Journal: bioRxiv

Article Title: GLP-1R Agonism Directly Improves the Pumping Capacity of Murine Collecting Lymphatic Vessels

doi: 10.64898/2025.12.26.696603

Figure Lengend Snippet: (A) Representative diameter trace of an inguinal axillary lymphatic vessel displaying the functional response to increasing concentrations of semaglutide in the range of 1nM to 1µM; the contractile activity was assessed for 5 minutes at each concentration; (B-I) Mean contractile parameters as a function of semaglutide concentration (expressed as mean±SEM), including (B) amplitude, (C) end diastolic diameter (EDD), (D) end systolic diameter (ESD), (E) ejection fraction, (F) contraction frequency, (G) width, (H) fractional pump flow (FPF), and (I) volume displaced. A total of n=17 vessels were included and a one-way ANOVA test that included a correction for multiple comparisons using Dunnett’s test and a Geisser-Greenhouse correction as no equal variances were assumed (i.e., sphericity was not assumed) were used to determine differences in contractile function parameters, with statistical significance set at p<0.05.

Article Snippet: The cellular localization of GLP-1Rs in collecting lymphatic vessels was assessed using semaglutide conjugated with FITC (Cat. No.: HY-114118F, MedChemExpress).

Techniques: Functional Assay, Activity Assay, Concentration Assay

Journal: bioRxiv

Article Title: GLP-1R Agonism Directly Improves the Pumping Capacity of Murine Collecting Lymphatic Vessels

doi: 10.64898/2025.12.26.696603

Figure Lengend Snippet: (A) Representative diameter trace displaying the contractile activity of an inguinal axillary lymphatic vessel from a WT mouse under control conditions and following stimulation with a single 5 nM dose of semaglutide. (B-I) Summary data of different contractile parameters before (Ctrl) and after 5nM stimulus with semaglutide (Sema), including (B) amplitude, (C) end diastolic diameter (EDD), (D) end systolic diameter (ESD), (E) ejection fraction, (F) contraction frequency, (G) width, (H) fractional pump flow (FPF), (I) volume displaced, and (J) volume displaced for each individual contraction in panel A. A total of n=11 vessels were used for these experiments and paired parametric T test was used to determine significance, with statistical significance set at p<0.05.

Article Snippet: The cellular localization of GLP-1Rs in collecting lymphatic vessels was assessed using semaglutide conjugated with FITC (Cat. No.: HY-114118F, MedChemExpress).

Techniques: Activity Assay, Control

Journal: bioRxiv

Article Title: GLP-1R Agonism Directly Improves the Pumping Capacity of Murine Collecting Lymphatic Vessels

doi: 10.64898/2025.12.26.696603

Figure Lengend Snippet: (A) Representative diameter trace displaying the contractile activity of an inguinal axillary lymphatic vessel from a WT mouse under control conditions, during a 20-minute pre-treatment with L-NAME (100µM) and indomethacin (10µM), and after stimulation with a single 5 nM dose of semaglutide. (B-I) Summary data of different contractile parameters under these 3 paired conditions, including (B) amplitude, (C) end diastolic diameter (EDD), (D) end systolic diameter (ESD), (E) ejection fraction, (F) contraction frequency, (G) width, (H) fractional pump flow (FPF), and (I) volume displaced. A total of n=11 vessels from WT mice were used for these experiments. A one-way ANOVA corrected with a Geisser-Greenhouse correction as no equal variances were assumed (i.e., sphericity was not assumed) was used to determine differences in contractile function parameters, with statistical significance set at p<0.05.

Article Snippet: The cellular localization of GLP-1Rs in collecting lymphatic vessels was assessed using semaglutide conjugated with FITC (Cat. No.: HY-114118F, MedChemExpress).

Techniques: Activity Assay, Control

Journal: bioRxiv

Article Title: GLP-1R Agonism Directly Improves the Pumping Capacity of Murine Collecting Lymphatic Vessels

doi: 10.64898/2025.12.26.696603

Figure Lengend Snippet: (A) Representative diameter trace displaying the contractile activity of an inguinal axillary lymphatic vessel from a WT mouse under control conditions, during a 20-minute pre-treatment with L-NAME (100µM), indomethacin (10µM), and apocynin (100µM), and after stimulation with a single 5 nM dose of semaglutide. (B-I) Summary data of different contractile parameters under these 3 paired conditions, including (B) amplitude, (C) end diastolic diameter (EDD), (D) end systolic diameter (ESD), (E) ejection fraction, (F) contraction frequency, (G) width, (H) fractional pump flow (FPF), and (I) volume displaced. A total of n=11 vessels from WT mice were used for these experiments. A one-way ANOVA corrected with a Geisser-Greenhouse correction as no equal variances were assumed (i.e., sphericity was not assumed) was used to determine differences in contractile function parameters, with statistical significance set at p<0.05.

Article Snippet: The cellular localization of GLP-1Rs in collecting lymphatic vessels was assessed using semaglutide conjugated with FITC (Cat. No.: HY-114118F, MedChemExpress).

Techniques: Activity Assay, Control

Journal: bioRxiv

Article Title: GLP-1R Agonism Directly Improves the Pumping Capacity of Murine Collecting Lymphatic Vessels

doi: 10.64898/2025.12.26.696603

Figure Lengend Snippet: Summary data of contractile parameters characterizing the contractile function of lymphatic vessels from WT, DIO, and ApoE KO mice under control conditions and following perfusion with a Krebs buffer containing 5 nM semaglutide. These contractile parameters are expressed as mean±SEM and include (A) contraction amplitude, (B) end diastolic diameter (EDD), (C) end systolic diameter (ESD), (D) ejection fraction, (E) contraction frequency, (F) contraction width (at half maximum), (G) fractional pump flow (FPF), and (H) volume displaced. A total of n=17 (control) and n=10 (sema) vessels from WT mice, n=13 (control) and n=12 (sema) vessels for DIO mice, and n=19 (control) and n=9 (sema) vessels from ApoE KO mice were used for these experiments. A two-way ANOVA was utilized to assess differences in contractile parameters with statistical significance set as p<0.05.

Article Snippet: The cellular localization of GLP-1Rs in collecting lymphatic vessels was assessed using semaglutide conjugated with FITC (Cat. No.: HY-114118F, MedChemExpress).

Techniques: Control