| Full text | |
| Author(s): Show less - |
Lindstedt, Philip R.
[1]
;
Aprile, Francesco A.
[1]
;
Matos, Maria J.
[1]
;
Perni, Michele
[1]
;
Bertoldo, Jean B.
[1]
;
Bernardim, Barbara
[1]
;
Peter, Quentin
[1]
;
Jimenez-Oses, Gonzalo
[2, 3]
;
Knowles, Tuomas P. J.
[1]
;
Dobson, Christopher M.
[1]
;
Corzana, Francisco
[3]
;
Vendruscolo, Michele
[1]
;
Bernardes, Goncalo J. L.
[4, 1]
Total Authors: 13
|
| Affiliation: | [1] Univ Cambridge, Dept Chem, Ctr Misfolding Dis, Lensfield Rd, Cambridge CB2 1EW - England
[2] CIC bioGUNE, Bizkaia Technol Pk, Bldg 801A, Derio 48170 - Spain
[3] Univ La Rioja, Ctr Invest Sintesis Quim, Dept Quim, Logrono 26006 - Spain
[4] Univ Lisbon, Fac Med, Inst Med Mol, Ave Prof Egas Moniz, P-1649028 Lisbon - Portugal
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | ACS CENTRAL SCIENCE; v. 5, n. 8, p. 1417-1424, AUG 28 2019. |
| Web of Science Citations: | 1 |
| Abstract | |
Protein behavior is closely regulated by a plethora of post-translational modifications (PTMs). It is therefore desirable to develop approaches to design rational PTMs to modulate specific protein functions. Here, we report one such method, and we illustrate its successful implementation by potentiating the anti-aggregation activity of a molecular chaperone. Molecular chaperones are a multifaceted class of proteins essential to protein homeostasis, and one of their major functions is to combat protein misfolding and aggregation, a phenomenon linked to a number of human disorders. In this work, we conjugated a small-molecule inhibitor of the aggregation of alpha-synuclein, a process associated with Parkinson's disease (PD), to a specific cysteine residue on human Hsp70, a molecular chaperone with five free cysteines. We show that this regioselective conjugation augments in vitro the anti-aggregation activity of Hsp70 in a synergistic manner. This Hsp70 variant also displays in vivo an enhanced suppression of alpha-synuclein aggregation and its associated toxicity in a Caenorhabditis elegans model of PD. (AU) | |
| FAPESP's process: | 17/13168-8 - Construction of chemically defined antibody-drug conjugates using carbonylacrylic reagents |
| Grantee: | Barbara Bernardim de Souza |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |