molecules-logo

Journal Browser

Journal Browser

Thrombin Inhibitors: Discovery and Design

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (20 December 2015) | Viewed by 17088

Special Issue Editor


E-Mail Website
Guest Editor
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
Interests: structure-function relationships in natural thrombin inhibitors

Special Issue Information

Dear Colleagues,

Playing a myriad of procoagulant and anticoagulant roles, thrombin is a central effector in haemostasis and a focal point for blood clotting control, including therapeutic intervention. Given its significant structural similarity to many other serine proteinases carrying out a multitude of disparate tasks, controlling thrombin's behavior with small chemical compounds without interfering with the activity of related enzymes is a formidable challenge. There are, however, many examples of extremely potent and specific thrombin-targeting molecules, namely in the form of natural anticoagulants from haematophagous organisms or from other biological sources. Over the years, many of the unique thrombin recognition and inhibition strategies displayed by these molecules have been unveiled, all while many other synthetic inhibitors have been conceived, developed and perfected. As our knowledge mounts, every new generation of direct thrombin inhibitors brings us closer to the ultimate goal of safely and efficiently modulate thrombin’s activity in a clinical setting. This Special Issue is set to bring together the leading researchers in the fields of discovery and design of specific thrombin inhibitors, helping to disseminate the latest research results and serving as a hub for the establishment of novel and fruitful interactions and collaborations. Original research papers dealing with the discovery, design, characterization, and synthesis of specific thrombin inhibitors are welcome.

Dr. Pedro J. B. Pereira
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind 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 semimonthly 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 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


Keywords

  • Anticoagulant
  • Inhibitor
  • thrombin inhibition
  • serine proteinase
  • structure-guided drug design
  • structure-function relationships
  • drug discovery
  • haemostasis
  • blood clotting
  • macromolecular recognition
  • macromolecular interactions

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

1423 KiB  
Article
Design of Potent and Controllable Anticoagulants Using DNA Aptamers and Nanostructures
by Abhijit Rangnekar, Jessica A. Nash, Bethany Goodfred, Yaroslava G. Yingling and Thomas H. LaBean
Molecules 2016, 21(2), 202; https://doi.org/10.3390/molecules21020202 - 06 Feb 2016
Cited by 19 | Viewed by 6140
Abstract
The regulation of thrombin activity offers an opportunity to regulate blood clotting because of the central role played by this molecule in the coagulation cascade. Thrombin-binding DNA aptamers have been used to inhibit thrombin activity. In the past, to address the low efficacy [...] Read more.
The regulation of thrombin activity offers an opportunity to regulate blood clotting because of the central role played by this molecule in the coagulation cascade. Thrombin-binding DNA aptamers have been used to inhibit thrombin activity. In the past, to address the low efficacy reported for these aptamers during clinical trials, multiple aptamers have been linked using DNA nanostructures. Here, we modify that strategy by linking multiple copies of various thrombin-binding aptamers using DNA weave tiles. The resulting constructs have very high anticoagulant activity in functional assays owing to their improved cooperative binding affinity to thrombin due to optimized spacing, orientation, and the high local concentration of aptamers. We also report the results of molecular dynamics simulations to gain insight into the solution conformations of the tiles. Moreover, by using DNA strand displacement, we were able to turn the coagulation cascade off and on as desired, thereby enabling significantly better control over blood coagulation. Full article
(This article belongs to the Special Issue Thrombin Inhibitors: Discovery and Design)
Show Figures

Graphical abstract

Review

Jump to: Research

730 KiB  
Review
New Approaches to the Role of Thrombin in Acute Coronary Syndromes: Quo Vadis Bivalirudin, a Direct Thrombin Inhibitor?
by María Asunción Esteve-Pastor, Diana Hernández-Romero, Mariano Valdés and Francisco Marín
Molecules 2016, 21(3), 284; https://doi.org/10.3390/molecules21030284 - 27 Feb 2016
Cited by 2 | Viewed by 10635
Abstract
The pathophysiology of acute coronary syndrome (ACS) involves platelet activation and thrombus formation after the rupture of atherosclerotic plaques. Thrombin is generated at the blood-plaque interface in association with cellular membranes on cells and platelets. Thrombin also amplifies the response to the tissue [...] Read more.
The pathophysiology of acute coronary syndrome (ACS) involves platelet activation and thrombus formation after the rupture of atherosclerotic plaques. Thrombin is generated at the blood-plaque interface in association with cellular membranes on cells and platelets. Thrombin also amplifies the response to the tissue injury, coagulation and platelet response, so the treatment of ACS is based on the combined use of both antiplatelet (such as aspirin, clopidogrel, prasugrel and ticagrelor) and antithrombotic drugs (unfractionated heparin, enoxaparin, fondaparinux and bivalirudin). Bivalirudin competitively inhibits thrombin with high affinity, a predictable response from its linear pharmacokinetics and short action. However, a present remarkable controversy exists between the latest main Guidelines in Clinical Practice and the key trials evaluating the use of bivalirudin in ACS. The aim of this review is to update the development of bivalirudin, including pharmacological properties, obtained information from clinical trials evaluating efficacy and safety of bivalirudin in ACS; as well as the recommendations of clinical Guidelines. Full article
(This article belongs to the Special Issue Thrombin Inhibitors: Discovery and Design)
Show Figures

Figure 1

Back to TopTop