Special Issue "Peptidomimetics"
A special issue of Pharmaceuticals (ISSN 1424-8247).
Deadline for manuscript submissions: closed (31 August 2011)
Prof. Dr. Andrew Abell
School of Chemistry & Physics, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia
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. Pharmaceuticals 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 500 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
Pharmaceuticals 2011, 4(9), 1248-1280; doi:10.3390/ph4091248
Received: 29 August 2011; in revised form: 9 September 2011 / Accepted: 15 September 2011 / Published: 21 September 2011| Download PDF Full-text (601 KB) | Download XML Full-text
Pharmaceuticals 2012, 5(2), 209-235; doi:10.3390/ph5020209
Received: 16 December 2011; in revised form: 17 January 2012 / Accepted: 19 January 2012 / Published: 16 February 2012| Download PDF Full-text (665 KB) | Download XML Full-text
Pharmaceuticals 2012, 5(3), 297-316; doi:10.3390/ph5030297
Received: 27 December 2011; in revised form: 22 February 2012 / Accepted: 28 February 2012 / Published: 8 March 2012| Download PDF Full-text (466 KB) | Download XML Full-text
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Article
Title: Novel Approach to Antithrombotic Development: Macromolecular Hyperbranched Polyglycerol Targeted with VWF-Derived Peptide Enantiomers
Authors: Jerry G. Zhang 1,2,3, Carlos A. del Carpio 4, Peter Schubert 1,2,3, Rajesh K. Kainthan 2,3, Jayachandran N. Kizhakkedathu 2,3, Donald E. Brooks 2,3, William Campbell 5 and Maria I. C. Gyongyossy-Issa 2,3
Affiliations: 1 Canadian Blood Services
2 Department of Pathology and Laboratory Medicine
3 Centre for Blood Research
4 Department of Applied Chemistry, Tohoku University, Sendai, Japan
5 Brain Research Centre, University of British Columbia, Vancouver, Canada
Abstract: Background and objectives: Glycoprotein GPIb’s interaction with von Willebrand factor (VWF), an early step of platelet activation and clot formation, is an ideal target for development of a new generation of antithrombotics. Methods: Using bioinformatic tools, we mapped the binding surface of GPIb for VWF, then generated a peptide inhibitor array to the GPIb-VWF interaction based on the native sequence of the VWF A1 domain. MIAX software “soft-docked” inhibitory 10-mer peptides onto GPIb then calculated the energy of binding. Based on its binding location on GPIb, the peptide SHAYIGLKDR was selected and synthesized in L-, L-retro, D-, and D-retro forms and tested free in solution or conjugated to a 500 kDa hyperbranched polyglycerol (HPG) as macromolecular carrier. Results: SHAYIGLKDR’s L- and L-retro forms inhibited GPIb-VWF interactions and subsequent signal transduction. Disruption of ristocetin-mediated VWF binding to platelets and platelet agglutination was achieved at IC50 = 5 x 10-5 M. Conjugation to HPG at ratios of 10:1 and 100:1 (peptide:carrier), enhanced inhibition by orders of magnitude proportionate to the peptide:carrier ratio, to IC50 at 3 x 10-7 M. Conclusion: These results create a new approach to antithrombotic development using peptides to specifically target the GPIb-VWF interaction surface with HPG as the macromolecular carrier to enhance effectiveness by both polyvalency and steric inhibition.
Last update: 1 April 2011