Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.55 (PTR)
 433 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin, also known as somatotropin release-inhibiting factor (SRIF), is a natural cyclic peptide inhibitor of pituitary, pancreatic, and gastrointestinal secretion. Its long-acting analogs are in clinical use for treatment of various endocrine syndromes and gastrointestinal anomalies. These analogs are more potent inhibitors of the endocrine release of GH, glucagon, and insulin than the native SRIF; hence, they do not display considerable physiological selectivity. Our goal was to design effective and physiologically selective SRIF analogs with potential therapeutic value. We employed an integrated approach consisting of screening of backbone cyclic peptide libraries constructed on the basis of molecular modeling of known SRIF agonists and of high throughput receptor binding assays with each of the five cloned human SRIF receptors (hsst1-5). By using this approach, we identified a novel, high affinity, enzymatically stable, and long-acting SRIF analog, PTR-3173, which binds with nanomolar affinity to human SRIF receptors hsst2, hsst4, and hsst5. The hsst5 and the rat sst5 (rsst5) forms have the same nanomolar affinity for this analog. In the human carcinoid-derived cell line BON-1, PTR-3173 inhibits forskolin-stimulated cAMP accumulation as efficiently as the drug octreotide, indicating its agonistic effect in this human cell system. In hormone secretion studies with rats, we found that PTR-3173 is 1000-fold and more than 10,000-fold more potent in inhibiting GH release than glucagon and insulin release, respectively. These results suggest that PTR-3173 is the first highly selective somatostatinergic analog for the in vivo inhibition of GH secretion, with minimal or no effect on glucagon and insulin release, respectively.
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PMID:Novel long-acting somatostatin analog with endocrine selectivity: potent suppression of growth hormone but not of insulin. 1114 12

Non-ionic surfactants have raised a considerable interest for solubilization, encapsulation, permeabilization and controlled release of various compounds due to their unique physicochemical properties. Nevertheless, it is still challenging to create convenient self-assembled multifunctional materials with high solubilization and encapsulation capacities by preserving their advanced capabilities to protect loaded cargos without altering their characteristics. In this work, we present an extended concept of micellar clusters (MCs) formation based on partial entrapment and stabilization of chelate ligands by hydrophobic forces found on the non-ionic surfactant micelle interface of the Triton-X family (TX-100/TX-114), followed by subsequent complexation of the preformed structures either by metal ions or a supporting chelator. The formation aspects, inner structure and the role of external factors such as the addition of competitive ligands have been extensively studied. MCs loaded by hydrophobic fluorescent compounds with high encapsulation efficiency demonstrate an excellent optical response in aqueous media without crystallization as well as sufficient increase in solubility of toxic hydrophobic compounds such as bilirubin (>50 times compared to pure surfactants). Furthermore, Triton-X-based MCs provide a unique feature of selective permeability to hydrophilic ligand-switching proteins such as UnaG and BSA demonstrating bright "turn-on" fluorescence signal either inside the cluster or on its interface via complexation. The proposed strategies allowed us to successfully encapsulate and visualize a newly synthesized, highly hydrophobic anticancer PTR-58-CLB-CAMP peptide drug, while MCs loaded by the drug exhibit a considerable antitumor activity against HeLa cells.
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PMID:Self-assembled micellar clusters based on Triton-X-family surfactants for enhanced solubilization, encapsulation, proteins permeability control, and anticancer drug delivery. 3088 54