Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
Por:
Sánchez, JM, López-Laguna, H, Parladé, E, Somma, AD, Livieri, AL, Alamo, P, Mangues, R, Unzueta, U, Villaverde, A, Vázquez, E
Publicada:
19 mar 2024
Ahead of Print:
1 mar 2024
Resumen:
Developing time-sustained drug delivery systems is a main goal in innovative medicines. Inspired by the architecture of secretory granules from the mammalian endocrine system it has generated non-toxic microscale amyloid materials through the coordination between divalent metals and poly-histidine stretches. Like their natural counterparts that keep the functionalities of the assembled protein, those synthetic structures release biologically active proteins during a slow self-disintegration process occurring in vitro and upon in vivo administration. Being these granules formed by a single pure protein species and therefore, chemically homogenous, they act as highly promising time-sustained drug delivery systems. Despite their enormous clinical potential, the nature of the clustering process and the quality of the released protein have been so far neglected issues. By using diverse polypeptide species and their protein-only oligomeric nanoscale versions as convenient models, a conformational rearrangement and a stabilization of the building blocks during their transit through the secretory granules, being the released material structurally distinguishable from the original source is proved here. This fact indicates a dynamic nature of secretory amyloids that act as conformational arrangers rather than as plain, inert protein-recruiting/protein-releasing granular depots.
Polypeptides incorporated into artificial secretory amyloids, by the coordination between Zn2+ and histidine-rich tails, undergo a conformation modification by which the protein gains structural stability, associated to a better secretory performance. These data offer clues for the mechanistic understanding of amyloidal depots with secretory properties and for the fabrication of high-performance versions for clinical applications. image
Filiaciones:
Sánchez, JM:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Placa Civica S-N, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Placa Civica S-N, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08024, Spain
Univ Nacl Cordoba, Inst Invest Biol & Tecnol IIBYT, ICTA, FCEFyN,CONICET,UNC, Av Velez Sarsfield 1611,X5016GCA, Cordoba, Argentina
López-Laguna, H:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Placa Civica S-N, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Placa Civica S-N, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08024, Spain
Parladé, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Placa Civica S-N, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08024, Spain
Somma, AD:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Placa Civica S-N, Barcelona 08193, Spain
Univ Naples Federico II, Dept Chem Sci, Vicinale Cupa Cintia 26, I-80126 Naples, Italy
CEINGE Adv Biotechnol, Via Gaetano Salvatore 486, I-80145 Naples, Italy
Livieri, AL:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Placa Civica S-N, Barcelona 08193, Spain
Alamo, P:
Inst Recerca St Pau IR St Pau, Sant Quinti 77-79, Barcelona 08041, Spain
Mangues, R:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08024, Spain
Inst Recerca St Pau IR St Pau, Sant Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Unzueta, U:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Placa Civica S-N, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08024, Spain
Inst Recerca St Pau IR St Pau, Sant Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Placa Civica S-N, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Placa Civica S-N, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08024, Spain
Vázquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Placa Civica S-N, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Placa Civica S-N, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08024, Spain
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