A5040759041- Chemical Synthesis and Analysis
- Neuropeptides and Animal Physiology
- Carbohydrate Chemistry and Synthesis
- Diabetes Treatment and Management
- Receptor Mechanisms and Signaling
- Protein Hydrolysis and Bioactive Peptides
- Biochemical and Structural Characterization
- Glycosylation and Glycoproteins Research
- Growth Hormone and Insulin-like Growth Factors
- Probiotics and Fermented Foods
- Axon Guidance and Neuronal Signaling
- Antimicrobial Peptides and Activities
- Microbial Metabolites in Food Biotechnology
- Supramolecular Self-Assembly in Materials
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Neuroendocrine regulation and behavior
- Nicotinic Acetylcholine Receptors Study
- RNA Interference and Gene Delivery
- Neuroscience of respiration and sleep
- Alkaloids: synthesis and pharmacology
- Asymmetric Synthesis and Catalysis
- Bone Metabolism and Diseases
California Institute for Biomedical Research
2019-2022
Scripps (United States)
2019-2022
Scripps Institution of Oceanography
2019-2022
Scripps Research Institute
2019-2020
University of Auckland
2014-2018
Maurice Wilkins Centre
2014-2017
Replacing the <italic>O</italic>-linked saccharide in bacteriocin glycocin F with an <italic>S</italic>-linked version results a peptidomimetic that increases bacteriostatic effect.
Existing long α-helix mimicking necessitates the retention of most natural amino acid residues to maintain their biological activity. Here, we report exploration helical sulfono-γ-AApeptides with entire unnatural backbones for ability structurally and functionally mimic glucagon-like peptide 1 (GLP-1). Our findings suggest that efficient construction novel GLP-1 receptor (GLP-1R) agonists could be achieved nanomolar potencies. In addition, resulting were also proved display remarkable...
Glycosyl thiols may be accessed from the corresponding reducing sugars in water without recourse to any sugar projecting groups by way of a DMC mediated reaction with thioacetic acid presence base, and hydrolysis anomeric thioacetate. produced this method used access glycoconjugates, such as glycopeptides use thiol-ene click reaction.
Oxyntomodulin (OXM) is an intestinal peptide hormone that activates both glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors. The natural reduces body weight in obese subjects exhibits direct acute glucoregulatory effects patients with type II diabetes. However, the clinical utility of OXM limited due to its lower vitro potency short vivo half-life. To overcome these issues, we developed stapled, long-acting, highly potent analogs balanced activities at GLP-1 GCG lead molecule O14...
Glycocin F, a bacteriocin produced by Lactobacillus plantarum KW30, is glycosylated with two N-acetyl-d-glucosamine sugars, and has been shown to exhibit rapid reversible bacteriostasis on susceptible cells. The roles of certain structural features glycocin F have not studied date. We report here the synthesis various analogues through solid-phase peptide (SPPS) native chemical ligation (NCL), allowing us probe different this peptide. Our results indicate that bacteriostatic activity...
Preptin is a 34-residue pancreatic hormone shown to be anabolic bone in vitro and vivo. The activity of preptin resides within the (1-16) N-terminal fragment. Due its peptidic nature, truncated fragment enzymatically unstable; however it provides an attractive framework for creation stable analogues using various peptidomimetic techniques. An alanine scan was undertaken which showed that substitution Ser at position 3 or Pro 14 did not inhibit proliferative primary rat osteoblasts...
The first syntheses of the naturally occurring cyclic peptides dianthin I (1), pseudostellarin A (2), and heterophyllin J (3) are described. linear protected peptide precursors were prepared efficiently via Fmoc-solid-phase synthesis subsequently cyclized in solution under dilute conditions. structures synthetic cyclopentapeptides confirmed by NMR spectroscopy mass spectrometry agreement with literature data reported for natural products.
Dianthin G and its dicarba analogue were both shown to increase the number of human osteoblasts without affecting bone resorption.
The effects of oxytocin on food intake and body weight reduction have been demonstrated in both animal models human clinical studies. Despite being efficacious, is enzymatically unstable thus considered to be unsuitable for long-term use patients with obesity. Herein, a series derivatives were engineered through conjugation fatty acid moieties that are known exhibit high binding affinities serum albumin. One analog (OT-12) particular was shown potent full agonist at the receptor (OTR) vitro...
Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As natural agonist GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest the treatment type-2 diabetes mellitus, but its in vivo instability short half-life have largely prevented application. Here, we describe rational design series α/sulfono-γ-AA hybrid analogues GLP-1 as GLP-1R agonists....
Owing to their pleiotropic metabolic benefits, glucagon-like peptide-1 receptor (GLP-1R) agonists have been successfully utilized for treating diseases, such as type 2 diabetes and obesity. As part of our efforts in developing long-acting peptide therapeutics, we previously reported a engineering strategy that combines side chain stapling with covalent integration serum protein-binding motif single step. Herein, used this develop second generation extendin-4 analog rigidified symmetrical...
An improved solid-phase synthesis of the neuroprotective tripeptide, glycyl-prolyl-glutamic acid, bearing a hydrophobic tail to create an amphiphile is described. The new was adapted prepare several analogues differing tails.
e15113 Background: Ephrin type-A receptor 2 (EphA2) is a glycoprotein of the ephrin subfamily. EphA2 primarily involved in tissue patterning during embryonic development, and its expression levels are low or absent normal adult tissues. However, overexpression has been observed multiple malignant tumors such as bladder, cervical, ovarian, colorectal, lung esophageal cancers. In addition to being tumor biomarker, plays an active role survival, metastasis neo-angiogenesis, which can lead poor...