EventsMOL2NET'20, Conference on Molecular, Biomed., Comput. & Network Science and Engineering, 6th ed.
Event submissions
Published
with-doi10.3390/mol2net-06-08950 (registering DOI)
This submission belongs to the session 01. CHEMBIOMOL-06: Chem. Biol. & Med. Chem. Workshop, Bilbao-Rostock, Germany-Galveston, Texas, USA, 2020 of the event MOL2NET'20, Conference on Molecular, Biomed., Comput. & Network Science and Engineering, 6th ed.
Published date
07 Jan, 2021
Citation
Humbert Gonzalez-Diaz, Ivo Sampaio, Jose M Brea, Mabel Losa, Jose E Borges, Dolores Viña, Olga Caamaño, Xerardo García-Mera, PTML Computational Study, Synthesis, and Pharmacological Assay of MIF-1 Peptidomimetics, in Proceedings of MOL2NET'20, Conference on Molecular, Biomed., Comput. & Network Science and Engineering, 6th ed., 30 January 2020–30 January 2021, MDPI: Basel, Switzerland, doi: 10.3390/mol2net-06-08950
Share
Email
Facebook
Twitter
LinkedIn

PTML Computational Study, Synthesis, and Pharmacological Assay of MIF-1 Peptidomimetics

Ivo Sampaio 1
Jose E Borges 2
Jose M Brea 3
Dolores Viña 4
Mabel Losa 3
Olga Caamaño 5
image
Humbert Gonzalez-Diaz 6,7
Xerardo García-Mera 5
1. LAQV/REQUIMTE, Dept. of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
2. REQUIMTE/Department of Chemistry and Biochemistry, University of Porto, 4169-007 Porto, Portugal
3. Dept. of Pharmacology, Faculty of Medicine and Nursing, University of Basque Country (UPV-EHU), 48940 Leioa, Spain.
4. Department of Pharmacology, USC, 15782, Santiago de Compostela, Spain.
5. Department of Organic Chemistry, University of Santiago de Compostela (USC), 15782, Santiago de Compostela, Spain.
6. Department of Organic Chemistry II, University of the Basque Country (UPV/EHU), Biscay, Spain, Spain
7. IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain.
Abstract

In a recent work we described the organic synthesis and experimental pharmacological assay of MIF-1 peptidomimetics modulators of D2 receptors (D2R). We measured their ability to enhance the maximal effect of tritiated N-propylapomorphine ([3H]-NPA) at D2R. The 2-furoyl-l-leucylglycinamide (6a) showed increase maximal [3H]-NPA response at 10 pM (11 ± 1%) compared to MIF-1. Neurotoxicity assays of MIF-1 derivative 6a with cortex neurons of Wistar-Kyoto rat embryos suggest low neurotoxicity. Additionally, we reported a predictive model >20 000 outcomes of preclinical assays reported in ChEMBL for this kind of modulators. The model shows high specificity Sp = 89.2/89.4%, sensitivity Sn = 71.3/72.2%, and accuracy Ac = 86.1%/86.4% in training/validation series, respectively. The model is useful to predict this and similar compounds.

Ref: Synthesis, Pharmacological, and Biological Evaluation of 2-Furoyl-Based MIF-1 Peptidomimetics and the Development of a General-Purpose Model for Allosteric Modulators (ALLOPTML). Sampaio-Dias IE, Rodríguez-Borges JE, Yáñez-Pérez V, Arrasate S, Llorente J, Brea JM, Bediaga H, Viña D, Loza MI, Caamaño O, García-Mera X, González-Díaz H.ACS Chem Neurosci. 2021 Jan 6;12(1):203-215. doi: 10.1021/acschemneuro.0c00687. Epub 2020 Dec 21.PMID: 33347281

Keywords
MIF-1 peptidomimetics
D2R modulators
Organic synthesis
Neurotoxicity
Machine Learning
Manuscript
mol2net template.pdf
Poster
mol2net template.pdf
mol2net template.pdf
Modelos PTMLIF en la predicción de sistemas de nanopartículas decoradas con fármacos.
Bioinformatics-based of warfarin individualized medication research in cardiac surgery patients