Current Pharmaceutical Biotechnology - Volume 14, Issue 5, 2013

Among the currently available options for the treatment of chronic myeloid leukemia (CML), ATP-competitive tyrosine kinases inhibitors (Gleevec®, Dasatinib® and Nilotinib®) represent one of the most promising therapeutic approaches developed in the last 10-15 years. However, the initial enthusiasm generated by the high response rate to these drugs has been dampened by the development of resistance. The T315I muta Read More

The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the Read More

Peptides are ideally suited to mimic natural ligands and thereby function in an antagonistic or agonistic way. Furthermore they are able to physiologically disrupt functional complexes due to their small size and specific binding properties. Proteins form homo- or heteromeric (macro)molecular complexes and intricate networks by interacting with small molecules, peptides, nucleic acids or other proteins. On av Read More

In general, drug discovery in the therapeutic field of infectious disease has a stellar track record. And yet, subsets of pathogens, for example many classes of viruses other than HIV, HSV, influenza, and HCV, have been poorly addressed. In addition, the development of resistance remains a specter of great concern for almost all current chemotherapy directed against infectious diseases, including viruses. Within the viral life Read More

Poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribosylation) play essential roles in several biological processes, among which neoplastic transformation and telomere maintenance. In this paper, we review the poly(ADPribosylation) process together with the highly appealing use of PARP inhibitors for the treatment of cancer. In addition, we report our results concerning poly(ADP-ribosylation) in a cellular model syste Read More

Knowledge of three-dimensional structures of biological macromolecules is essential for a complete understanding of many biological processes. X-ray crystallography is the most widely used technique in structural biology and can provide highly detailed structures of proteins, nucleic acids or macromolecular complexes without any size limit. In the past decade, several recent advances in biological crystallography and automa Read More

Drug development is a long and expensive process. It starts from the identification of a small molecule (hit compound) endowed with the ability to suppress a cellular or viral enzyme essential for the development of a given disease and proceeds through subsequent rounds of structural changes and optimization until the desired pharmacological properties are reached (lead compound). At any point of the hit-to-lead opti Read More

Highly active antiretroviral therapy (HAART) dramatically has changed the course of HIV infection. Currently, this therapy involves the use of agents from at least two distinct classes of antivirals: a protease inhibitor in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs), or a non-nucleoside reverse transcriptase inhibitor (NNRTI) in combination with NRTIs. Recently, the third family of antivirals st Read More