Peptide Synthesis
David Andreu
Website
Research outline
Synthetic peptides are useful in many areas of biomedical research, including well-known applications such as immunogens (anti-peptide antibodies, vaccines), affinity capture and purification ligands, intracellular delivery shuttles or anti-infectives. Our facility performs custom peptide synthesis and downstream operations such as purification to user-defined specifications, conjugation to carrier proteins to generate antibodies or immobilization on affinity columns. During 2019-20 the facility has performed over 420 synthesis jobs, conjugations to carrier proteins for antibody production, and related tasks for more than 50 users, of which many of them are intramural (PRBB) and the vast majority are external (research institutes, biotech and pharma companies). Sizes have ranged from 5 to 60+ residues, with an average of 25. Purities up to >98% (HPLC) are routinely achieved, as well as user-defined modifications such as different end (N- and C-terminal) groups, disulfide formation (intra- or intermolecular), modified (D-amino acid, phosphorylated, acetylated, methylated) amino acids, plus biotinylation, lipidation, fluorescent tags, etc. The average turnover time for most jobs (including synthesis, HPLC purification, analytical documentation) is 1-2 weeks.
Current Projects
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ELECTROMED - Electrochemically-enabled high-throughput peptidomics for next-generation precision medicine (H2020-FETOPEN-2018-2020 (862539))
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NOVIRUSES2BRAIN - ''One size fits all'' unique drug to eradicate multiple viral species simultaneously from the central nervous system of co-infected individuals (H2020-FETOPEN-2018-2020 (828774))
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NOZIKA - Fighting Zika virus with antiviral peptides and conjugates translocating blood-placental and blood-brain barriers (“La Caixa” Foundation Health Research call 2017 HR17_00409)
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DENUVAC - Construcciones vacunales peptídicas mono y multivalentes contra la fiebre aftosa: producción optimizada y estudios de estructura, estabilidad y biodistribución (AGL2017-84097-C2-2-R)
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Fighting pain with cannabis avoiding side-effects (Fundació “LA CAIXA” PRODUCTE grants 2018 Knowledge Industry, CI18-00045).
Selected publications
- Pérez-Peinado C, Valle J, Freire JM, Andreu D (2020). Tumor Cell Attack by Crotalicidin (Ctn) and Its Fragment Ctn[15–34]: Insights into Their Dual Membranolytic and Intracellular Targeting Mechanism. ACS Chem. Biol. DOI: 10.1021/acschembio.0c00596 PMID: 33021779.
- Skalska J, Andrade V.M, Cena G.L, Harvey P.J, Gaspar D, Mello É.O, Henriques S.T, Valle J, Gomes V.M, Conceição K, Castanho M.A.R.B, Andreu D (2020) Synthesis, Structure, and Activity of the Antifungal Plant Defensin PvD1. J. Med. Chem; 63(17): 9391-9402. Doi: 10.1021/acs.jmedchem.0c00543. PMID: 32787086.
- Cavaco M, Pérez-Peinado C, Valle J, D. M. Silva R, D. G. Correia J, Andreu D, Castanho M A. R. B. and Neves V (2020). To What Extent Do Fluorophores Bias the Biological Activity of Peptides? A Practical Approach Using Membrane-Active Peptides as Models. Frontiers in Bioengineering and Biotechnology. 8, 552035. Doi: 10.3389/fbioe.2020.552035. PMID: 33015016.
- Picón-Pagès P, Bonet J, García-García J, Garcia-Buendia J, Gutierrez D, Valle J, Gómez-Casuso CES, Sidelkivska V , Alvarez A , Perálvarez-Marín A , Suades A, Fernàndez-Busquets X, Andreu D, Vicente R, Oliva B, Muñoz FJ (2019) . Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease. Comput Struct Biotechnol J. 17, 963-971. DOI: 10.1016/j.csbj.2019.06.017 PMID: 31360335.
- Araújo-Bazán L, Huecas S, Valle J, Andreu D, Andreu JM (2019). Synthetic developmental regulator MciZ targets FtsZ across Bacillus species and inhibits bacterial division. Molecular microbiology. 111, 965-980. DOI: 10.1111/mmi.14198 PMID: 30636070.
Team during 2019-20
- Technicians: Javier Valle, Yolanda Tor.