Synthesis and characterization of ester‐based prodrugs of glucagon‐like peptide 1

De, Arnab; DiMarchi, Richard D.

doi:10.1002/bip.21418

Cited by 14 publications

(10 citation statements)

References 26 publications

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“…There is increasing interest in benefits of dualspecificity peptide ligands that have activity at multiple glucagon-peptide family receptors, combining activity at GLP-1 and glucagon receptors (Day et al, 2009), or GLP-1 and GIP receptors (De and DiMarchi, 2010); these peptide agonists have shown promise in preclinical studies for obesity treatment with greater weight loss than seen with GLP-1 agonism alone (Day et al, 2009;De and DiMarchi, 2010). This dual targeting strategy is being pursued by companies, including Zealand Pharma and Transition Therapeutics.…”

Section: E Glucagon-like Peptide 1 Receptormentioning

confidence: 99%

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

Riddy¹,

Delerive²,

Summers³

et al. 2017

Pharmacol Rev

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G protein-coupled receptors (GPCRs) continue to be important discovery targets for the treatment of type 2 diabetes mellitus (T2DM). Many GPCRs are directly involved in the development of insulin resistance and -cell dysfunction, and in the etiology of inflammation that can lead to obesity-induced T2DM. This review summarizes the current literature describing a number of well-validated GPCR targets, but also outlines several new and promising targets for drug discovery. We highlight the importance of understanding the role of these receptors in the disease pathology, and their basic pharmacology, which will pave the way to the development of novel pharmacological probes that will enable these targets to fulfill their promise for the treatment of these metabolic disorders.

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Section: E Glucagon-like Peptide 1 Receptormentioning

confidence: 99%

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

Riddy¹,

Delerive²,

Summers³

et al. 2017

Pharmacol Rev

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“…Here we have demonstrated the use of gold nanoparticles for immobilization of urease, a technique that could potentially be used to immobilize other relevant proteins and bioactive peptides. [53][54][55] The surface of the gold-glutathione nanoconjugates designed with the aim of easy and efficient interac-tion with a range of biologically relevant molecules has been employed for the covalent immobilization of the enzyme urease. Immobilization has been attempted at different pH conditions so as to elucidate the effect of both pH and immobilization on the conformation and subsequent bioactivity of the enzyme.…”

Section: Resultsmentioning

confidence: 99%

pH‐dependent immobilization of urease on glutathione‐capped gold nanoparticles

Garg

Mozumdar

2014

J Biomedical Materials Res

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Urease is a nickel-dependent metalloenzyme that catalyzes the hydrolysis of urea to form ammonia and carbon dioxide. Although the enzyme serves a significant role in several detoxification and analytical processes, its usability is restricted due to high cost, availability in small amounts, instability, and a limited possibility of economic recovery from a reaction mixture. Hence, there is a need to develop an efficient, simple, and reliable immobilization strategy for the enzyme. In this study, the carboxyl terminated surface of glutathione-capped gold nanoparticles have been utilized as a solid support for the covalent attachment of urease. The immobilization has been carried out at different pH conditions so as to elucidate its effect on the immobilization efficiency and enzyme bioactivity. The binding of the enzyme has been quantitatively and qualitatively analyzed through techniques like ultraviolet-visible spectroscopy, intrinsic steady state fluorescence, and circular dichorism. The bioactivity of the immobilized enzyme was investigated with respect to the native enzyme under different thermal conditions. Recyclability and shelf life studies of the immobilized enzyme have also been carried out. Results reveal that the immobilization is most effective at pH of 7.4 followed by that in an acidic medium and is least in alkaline environment. The immobilized enzyme also exhibits enhance activity in comparison to the native form at physiological temperature. The immobilized urease (on gold glutathione nanoconjugates surface) can be effectively employed for biosensor fabrication, immunoassays and as an in vivo diagnostic tool in the future.

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“…Various delivery systems have been designed in the past for modulated delivery of active drugs (25,26). A glutathionemediated hepatic cell-specific drug delivery vehicle has been synthesised featuring a non-toxic gold core, PEG as the soft spacer, lactose as the target-specific moiety and 7-aminocoumarin 3-carboxylic acid as the bioactive fluorescent moiety.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of a Smart Gold Nano‐vehicle for Liver Specific Drug Delivery

Garg

Nandi

et al. 2013

AAPS PharmSciTech

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Abstract. Targeting drug formulations to specific tissues and releasing the bioactive content in response to a certain stimuli remains a significant challenge in the field of biomedical science. We have developed a nanovehicle that can be used to deliver "drugs" to "specific" tissues. For this, we have simultaneously modified the surface of the nanovehicle with "drugs" and "tissue-specific ligands". The "tissue-specific ligands" will target the nanovehicle to the correct tissue and release the "drug" of interest in response to specific stimuli. We have synthesised a "lactose surface-modified gold nanovehicle" to target liver cells and release the model fluorescent drug (coumarin derivative) in response to the differential glutathione concentration (between blood plasma and liver cells). Lactose is used as the liver-specific targeting ligand given the abundance of L-galactose receptors in hepatic cells. The coumarin derivative is used as a fluorescent tag as well as a linker for the attachment of various biologically relevant molecules. The model delivery system is compatible with a host of different ligands and hence could be used to target other tissues as well in future. The synthesised nanovehicle was found to be non-toxic to cultured human cell lines even at elevated non-physiological concentrations as high as 100 μg/mL. We discover that the synthesised gold-based nanovehicle shows considerable stability at low extracellular glutathione concentrations; however coumarin is selectively released at high hepatic glutathione concentration.

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Synthesis and characterization of ester‐based prodrugs of glucagon‐like peptide 1

Cited by 14 publications

References 26 publications

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

pH‐dependent immobilization of urease on glutathione‐capped gold nanoparticles

Synthesis of a Smart Gold Nano‐vehicle for Liver Specific Drug Delivery

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