■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Isatins As Privileged Molecules in Design and Synthesis of Spiro-Fused Cyclic Frameworks

Isolation and synthesis of biologically active carbazole alkaloids

Occurrence, Biogenesis, and Synthesis of Biologically Active Carbazole Alkaloids

Recent advances in the synthesis of biologically active spirooxindoles

Purpose – Given the greater recognition of the role played by small and medium‐sized enterprises (SMEs) within the European economy, this research aims to provide an insight into SME CSR practices. Within this scope, the objective is to identify accurately and extensively: CSR practices at the social, economic and environmental levels; the motivations, perceived benefits, existing obstacles; and the types of support and strategies that render possible an explanation of the factors which place the greatest restrictions on SME adoption of CSR practices.Design/methodology/approach – This research was realized through the completion of a questionnaire type inquiry structured around table‐based analysis. The questionnaire was sent out to a large sample of SMEs in Portugal.Findings – The main results demonstrate that, while CSR takes on an informal, non‐structured character, it has been incorporated into the daily management of such companies. Furthermore, contrary to what happens at large companies, CSR at SME...

CSR in SMEs: strategies, practices, motivations and obstacles

Cysteine proteases selectively catalyze the hydrolysis of peptide bonds. Uncontrolled, unregulated, or undesired proteolysis can lead to many disease states including emphysema, stroke, viral infections, cancer, Alzheimer's disease, inflammation, and arthritis. Cysteine proteases inhibitors thus have considerable potential utility for therapeutic intervention in a variety of disease states. This review emphasizes on the new developments from literature reports on Michael acceptors as potential cysteine protease inhibitors, namely vinyl sulfones, alpha,beta-unsaturated carbonyl derivatives and aza-peptides. These compounds irreversibly alkylate the active site cysteine residue via conjugate addition. Examples of Michael acceptors inhibitors that have already progressed to clinical testing are also presented.

Michael Acceptors as Cysteine Protease Inhibitors

http://oro.open.ac.uk/18939/1/Santos_et_al_accepted.pdf

Maria M. M. Santos

Papers

Recent advances in the synthesis of biologically active spirooxindoles

CSR in SMEs: strategies, practices, motivations and obstacles

Michael Acceptors as Cysteine Protease Inhibitors

Reaction of naphthoquinones with substituted nitromethanes. Facile synthesis and antifungal activity of naphtho[2,3- d]isoxazole-4,9-diones

Synthesis of novel spiropyrazoline oxindoles and evaluation of cytotoxicity in cancer cell lines.