Differential copper-guided architectures of amyloid β peptidomimetics modulate oxidation states and catalysis

Abstract

Orchestration of differential architectures of designer peptidomimetics that modulate metal oxidation states to perform multiple chemical transformations remains a challenge. Cu-chelation and self-assembly properties of amyloid β (Aβ14-23) peptide were...

Multifunctional molecules with a bipyridyl core ameliorate multifaceted amyloid toxicity

“…The concentration-dependent study indicated Cu 2+ -ligand complexation with 1 : 1 stoichiometry. 17 Compound 5 exhibited the highest binding affinity (K d = 0.55 mM) for Cu 2+ , which agrees with our design strategy. MALDI mass analysis of 5 and Cu 2+ showed a predominant m/z peak at 578.07 corresponding to [M + Cu 2+ ], and minor peaks at 654.63 and 716.16 corresponding to [M + 2Cu 2+ ] and [M + 3Cu 2+ ], respectively (Fig.…”

Cooperative dissolution of peptidomimetic vesicles and amyloid β fibrils

“…The incorporation of a rigid, proteolytically stable, and biocompatible kd unit imparts hydrogen bonding interactions while the pyrene moiety provides required π-π stacking and hydrophobic interactions. [8][9][10]42,[49][50][51] The presence of a kd unit in Aβ14-23 at specified positions helps overcome limitations faced by linear peptides and other large cyclic peptide-based molecules. 51 The 16 KLVFF 20 segment derived from Aβ42 is well-known for its ability to recognize Aβ42 aggregation.…”

“…The synthesis of all peptidomimetics was performed using established solid phase peptide synthesis (SPPS) procedures with Fmoc-rink amide resin as the solid support. 42 Amino acids and unnatural CDP-amino acid (kd) were coupled using HBTU/ HOBt as the activating reagent and DIPEA as the base in DMF. Fmoc deprotection was achieved using 20% piperidine in DMF (Scheme S1 ‡).…”

“…The rigid, proteolytically stable, and biocompatible kd unit was considered for its ability to form hydrogen bonding interactions, while the pyrene residue imparts π-π stacking and hydrophobic interactions. 8,42 Among these, Akd c Py and Akd m Py spontaneously formed vesicles in aqueous media. The physicochemical characterizations of these synthesized vesicles were performed using various microscopy and spectroscopy techniques.…”

Two-Dimensional Molecular Architectonics through Controlled Noncovalent Interactions: Structure, Functional Properties, and Applications

“…We developed a peptidomimetic ( 46) by incorporating CDP-based unnatural amino acid, cyclo(L-Lys-L-Asp) (kd), at the middle (M), N-, and C-termini of the amyloid β peptide fragment (Aβ14−23). 74 The kd unit with a rigid core structure, multiple hydrogen bonding, and metal coordinating sites (amide linkages) was introduced for its metal interaction ability, while the fluorophore pyrene (Py) at the N-terminal is useful for tracking the process of the metal binding-induced assembly of 46 due to its distinctive spectral characteristics. The addition of Cu II modulated the fibrillar assembly of 46 into 2D sheet architectures in two distinctive ways, namely, one-off addition and serial addition.…”