Special Issue "Chemical Libraries"

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Special Issue Information
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Published Papers

A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (30 June 2012)

Special Issue Editor

Guest Editor
Dr. Olivier Sperandio
Research Associate at Inserm, Inserm UMR-S973/MTi. Université Paris Diderot, Bâtiment Lamarck - 5ème étage, salle 526, 35 Rue Hélène Brion – 75205 Paris Cedex 13, France
Website: http://www.mti.univ-paris-diderot.fr
E-Mail: olivier.sperandio@inserm.fr
Interests: PPI (protein-protein interaction); i-PPI (inhibitors of protein-protein interactions); chemical space; drug-like compounds; chemical library screening; novel chemistry for PPI

Special Issue Information

Dear Colleagues,

Protein-protein interactions (PPI) are one of the next major class of therapeutic targets. There are approximately 650,000 PPI in humans for about 25,000 genes. The identification of drug-like modulators of these PPI represents a considerable challenge but conversely some unprecedent therapeutical and pharmacological benefits for human health. However, current techniques for experimental screening of commercial libraries, which usually allow the identification of new innovative compounds, have clearly demonstrated their limits on PPI. The main reason for these difficulties is the inadequacy of the chemical libraries used, which have been historically tailored for more conventional therapeutic targets. One of the major breakthroughs that may facilitate the identification of pharmacological compounds on PPI is a better understanding of the chemical space associated with them. The perspective of guiding the chemist and the biologist in their design of innovative chemistries for PPI and the creation of appropriate libraries is therefore of major importance.

This Special Issue on the design of chemical libraries for PPI represents an attractive forum to present innovative synthesis, rational design and cheminformatics analysis with the aim of facilitating the identification chemical probes on PPI for chemical biology and/or drug discovery projects. I strongly encourage authors to submit papers for this Special Issue, within the scope of Molecules. I hope that the topics covered will serve the chemists and biologists of the growing PPI community.

Dr. Olivier Sperandio
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).

Keywords

PPI (protein-protein interaction)
i-PPI (inhibitors of protein-protein interactions)
chemical space
drug-like compounds
chemical library screening
novel chemistry for PPI
chemoinformatics

Published Papers (2 papers)

Yahia Nasser Mabkhot, Abdullah Mohammad Al-Majid, Abdullah Saleh Alamary, Ismail Warad and Yamin Sedigi

Article: Reactions of Some New Thienothiophene Derivatives

Molecules 2011, 16(6), 5142-5148; doi:10.3390/molecules16065142

Received: 30 May 2011; in revised form: 15 June 2011 / Accepted: 15 June 2011 / Published: 21 June 2011

Show/Hide Abstract | Download PDF Full-text (170 KB)

Daniel Plano, Elena Ibáñez, Alfonso Calvo, Juan Antonio Palop and Carmen Sanmartín

Article: Novel Library of Selenocompounds as Kinase Modulators

Molecules 2011, 16(8), 6349-6364; doi:10.3390/molecules16086349

Received: 30 June 2011; in revised form: 20 July 2011 / Accepted: 22 July 2011 / Published: 27 July 2011

Show/Hide Abstract | Download PDF Full-text (710 KB) |

Abstract: Although the causes of cancer lie in mutations or epigenic changes at the genetic level, their molecular manifestation is the dysfunction of biochemical pathways at the protein level. The 518 protein kinases encoded by the human genome play a central role in various diseases, a fact that has encouraged extensive investigations on their biological function and three dimensional structures. Selenium (Se) is an important nutritional trace element involved in different physiological functions with antioxidative, antitumoral and chemopreventive properties. The mechanisms of action for selenocompounds as anticancer agents are not fully understood, but kinase modulation seems to be a possible pathway. Various organosulfur compounds have shown antitumoral and kinase inhibition effects but, in many cases, the replacement of sulfur by selenium improves the antitumoral effect of compounds. Although Se atom possesses a larger atomic volume and nucleophilic character than sulfur, Se can also formed interactions with aminoacids of the catalytic centers of proteins. So, we propose a novel chemical library that includes organoselenium compounds as kinase modulators. In this study thirteen selenocompounds have been evaluated at a concentration of 3 or 10 µM in a 24 kinase panel using a Caliper LabChip 3000 Drug Discover Platform. Several receptor (EGFR, IGFR1, FGFR1…) and non-receptor (Abl) kinases have been selected, as well as serine/threonine/lipid kinases (AurA, Akt, CDKs, MAPKs…) implicated in main cancer pathways: cell cycle regulation, signal transduction, angiogenesis regulation among them. The obtained results showed that two compounds presented inhibition values higher than 50% in at least four kinases and seven derivatives selectively inhibited one or two kinases. Furthermore, three compounds selectively activated IGF-1R kinase with values ranging from −98% to −211%. In conclusion, we propose that the replacement of sulfur by selenium seems to be a potential and useful strategy in the search of novel chemical compound libraries against cancer as kinase modulators.

Last update: 26 September 2012

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