ABSTRACT
A series of novel 8-amino-1,3-disubstituted-imidazo[1,5-a]pyrazines was designed and synthesized as IGF-IR inhibitors.
Subject(s)
Imidazoles/chemical synthesis , Imidazoles/pharmacology , Pyrazines/chemical synthesis , Pyrazines/pharmacology , Receptor, IGF Type 1/antagonists & inhibitors , Adenosine Triphosphate/metabolism , Animals , Area Under Curve , Binding Sites , Biological Availability , Crystallography, X-Ray , Databases, Protein , Half-Life , Indicators and Reagents , Mice , Models, Molecular , Protein-Tyrosine Kinases/antagonists & inhibitors , Structure-Activity RelationshipABSTRACT
Structural features of two weak inhibitors of the ZipA-FtsZ protein-protein interaction which were found to bind to overlapping but different areas of the key binding site were combined in one new series of carboxybiphenyl-indoles with improved inhibitory activity.
Subject(s)
Bacterial Proteins/metabolism , Carrier Proteins/metabolism , Cell Cycle Proteins/metabolism , Cytoskeletal Proteins/metabolism , Drug Design , Escherichia coli Proteins/metabolism , Indoles/chemistry , Indoles/pharmacology , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/chemistry , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/chemistry , Cell Cycle Proteins/antagonists & inhibitors , Cell Cycle Proteins/chemistry , Cytoskeletal Proteins/antagonists & inhibitors , Cytoskeletal Proteins/chemistry , Escherichia coli Proteins/antagonists & inhibitors , Escherichia coli Proteins/chemistry , Inhibitory Concentration 50 , Models, Molecular , Molecular Structure , Protein Binding/drug effects , Protein Structure, Tertiary , Structure-Activity RelationshipABSTRACT
Among the most frequent anaphylactic reactions to insects are those attributed to reduviid bugs. We report the purification and identification of the major salivary allergen of these insects. This 20-kDa protein (procalin) is a member of the lipocalin family, which includes salivary allergens from other invertebrates and mammals. An expression system capable of producing reagent quantities of recombinant allergen was developed in Saccharomyces cerevisiae. Antisera produced against recombinant protein cross-reacts with ELISA with salivary allergen. Recombinant Ag is also shown to react with sera from an allergic patient but not with control sera. By immunolocalization, the source of the salivary Ag is the salivary gland epithelium and its secretions.
Subject(s)
Allergens/genetics , Allergens/immunology , Invertebrate Hormones/genetics , Invertebrate Hormones/immunology , Protein Precursors/genetics , Protein Precursors/immunology , Salivary Proteins and Peptides/genetics , Salivary Proteins and Peptides/immunology , Triatoma/genetics , Triatoma/immunology , Amino Acid Sequence , Anaphylaxis/immunology , Animals , Base Sequence , Cloning, Molecular , DNA, Complementary/genetics , DNA, Complementary/isolation & purification , Gene Expression , Humans , Immunohistochemistry , Insect Bites and Stings/immunology , Insect Proteins , Lipocalins , Molecular Sequence Data , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Saccharomyces cerevisiae/genetics , Saliva/immunology , Salivary Glands/immunologyABSTRACT
Scaling of the exact function for the number of intramolecular nonbonded contacts in a single maximally compact linear homopolymer on hypercubic lattices is determined as a function of number N of monomers and dimension d. A representative maximally compact structure is designed and an exact recursive expression for the maximum number m(max) of contacts is derived from that design. The equivalent nonrecursive expression yields the asymptotic scaling of m(max) as (d-1)N-dN(Delta)+1, with Delta=(d-1)/d. Implications in polymer and protein studies are discussed.
