Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alanine and N-methylation scans together with molecular modelling were implemented in order to propose a binding conformation of the minimum active fragment of bombesin (BB), Ac-BB[7-14], to the gastrin releasing peptide (GRP) and neuromedin B (NMB) receptors. These data are also used to critically evaluate the previously proposed binding conformations such as alpha-helix and antiparallel beta-sheets. This shows that the previously reported conformations do not satisfy the experimental data. A new binding conformation of Ac-BB[7-14] is proposed consisting of three consecutive gamma-turns followed by a bend and finishing with two gamma-turns. This low energy conformation (analogous to a fragment of thymidylate synthase, 2TSC) of bombesin stabilized by five internal hydrogen bonds, and with the side chains of residues Trp8 and Leu13 held on the same side of the peptide, is in agreement with the experimentally observed data. This and the results of molecular modelling may aid in the synthesis of conformationally restricted high affinity bombesin analogues and/or high affinity template-based GRP or NMB receptor agonists and antagonists.
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PMID:Alanine scan and N-methyl amide derivatives of Ac-bombesin[7-14]. Development of a proposed binding conformation at the neuromedin B (NMB) and gastrin releasing peptide (GRP) receptors. 898 85

This past year has proved to be a relatively disappointing one for the development of agents that could improve the survival rates of patients with advanced pancreatic cancer. A well designed randomized trial of treatment of patients with gemcitabine with or without a farnesyl transferase inhibitor (tried because pancreatic cancers have a high incidence of K- abnormalities) showed no improvement in survival rates. A definitive randomized controlled trial with a histone deacetylase inhibitor also proved negative. There are some signs of hope in that in early nonrandomized studies there are some new agents that appear to have some activity against the disease. These agents include the thymidylate synthase inhibitor capecitabine (which is possibly activated at the tumor site), the antigastrin immunogen G17DT (which is an immunization designed to neutralize the pancreatic growth factor gastrin), and the topoisomerase I inhibitor 9-nitrocamptothecin. In addition, the combination of the new agent oxaliplatin to high-dose 5FU plus leucovorin, which gave a median survival rate of 12.5 months, is also worthy of further study. Supportive care findings of interest for the patient with advanced pancreatic cancer of note include: the study in which eicosapentaenoic acid (fish oil) caused a modest weight gain (median of 1 kg), and the finding that ofloxacin plus ursodeoxycholic acid was not superior to ursodeoxycholic acid alone for the prevention or occlusion of biliary stents.
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PMID:New drugs for patients with pancreatic cancer. 1240 52