0000000000307280
AUTHOR
Inmaculada Conejos-sánchez
Targeting Alzheimer’s disease with multimodal polypeptide-based nanoconjugates
LRP1-targeted St-Cl–polyglutamate conjugates as multivalent neuroprotective/neurotrophic therapeutics for Alzheimer’s disease.
A controlled and versatile NCA polymerization method for the synthesis of polypeptides
A versatile and simple methodology for the preparation of well-defined polyglutamate nanocarriers is described. For the first time ammonium salts with non-nucleophilic tetrafluoroborate anions are used as initiators for the ring opening polymerization of alpha-N-carboxyanhydrides (NCAs) allowing a multigram scale polyglutamate synthesis with defined molecular weight (up to 800 units), low polydispersity (<1.2), controlled chain end functionality and adequate stereoselectivity and absence of any trace of toxic impurity to allow biomedical applications.
Polymer-doxycycline conjugates as fibril disrupters: an approach towards the treatment of a rare amyloidotic disease.
The term amyloidosis describes neurological diseases where an abnormal protein is misfolded and accumulated as deposits in organs and tissues, known as amyloid, disrupting their normal function. In the most common familial amyloid polyneuropathy (FAP), transthyretin (TTR) displays this role primarily affecting the peripheral nervous system (PNS). Advanced stages of this inherited rare amyloidosis, present as fibril deposits that are responsible for disease progression. In order to stop disease progression, herein we designed an efficient family of nanoconjugates as fibril disrupters. These polymer conjugates are based on doxycycline (doxy), already in phase II trials for Alzheimer's disease…