Comparative studies on peptides representing the so-called tachykinin-like region of the Alzheimer Aβ peptide [Aβ(25–35)]

In an attempt to answer the question of whether or not the so-called tachykinin-like region of the Alzheimer β-amyloid protein [Aβ(25–35)] can act as a tachykinin, the sequences Aβ(25–35), Aβ(25–35)amide and their norleucine-35 and phenylalanine-31 analogues were synthesized. These peptides were examined with ligand binding studies, electron microscopy, CD and NMR. In all cases some differences were found between the Aβ(25–35) analogue and the corresponding Phe31 peptide. In addition, in ligand displacement studies on tachykinin NK1 receptors, only the Phe31 analogue showed activity comparable to that of genuine tachykinins. We conclude that peptides based on Aβ(25–35) but with a Phe residue at position 31 do display properties typical of a tachykinin, but that peptides with Ile at this position do not.

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Electron Microscopy and X-ray Diffraction Studies further Confirm the Efficacy of PTI-00703® (Cat's Claw Derivative) as a Potential Inhibitor of Alzheimer's β-Amyloid Protein Fibrillogenesis

Alzheimer's Disease ◽

10.1002/0470846453.ch40 ◽

2003 ◽

pp. 449-460 ◽

Cited By ~ 1

Author(s):

Gerardo M. Castillo ◽

Daniel A. Kirschner ◽

Ann G. Yee ◽

Alan D. Snow

Keyword(s):

Electron Microscopy ◽

Amyloid Protein ◽

X Ray Diffraction ◽

X Ray ◽

Potential Inhibitor ◽

Β Amyloid

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Engineered interdomain disulfide in the periplasmic receptor for sulfate transport reduces flexibility. Site-directed mutagenesis and ligand-binding studies.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)67775-6 ◽

1991 ◽

Vol 266 (8) ◽

pp. 5220-5225

Author(s):

B L Jacobson ◽

J J He ◽

P S Vermersch ◽

D D Lemon ◽

F A Quiocho

Keyword(s):

Ligand Binding ◽

Site Directed Mutagenesis ◽

Directed Mutagenesis ◽

Sulfate Transport ◽

Binding Studies

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Interbase-FRET binding assay for pre-microRNAs

Scientific Reports ◽

10.1038/s41598-021-88922-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mattias Bood ◽

Anna Wypijewska del Nogal ◽

Jesper R. Nilsson ◽

Fredrik Edfeldt ◽

Anders Dahlén ◽

...

Keyword(s):

Ligand Binding ◽

Drug Targets ◽

Structural Changes ◽

Small Sample Size ◽

Resonance Energy ◽

Small Sample ◽

Titration Calorimetry ◽

Drug Candidate ◽

Binding Studies ◽

Aberrant Expression

AbstractThe aberrant expression of microRNAs (miRs) has been linked to several human diseases. A promising approach for targeting these anomalies is the use of small-molecule inhibitors of miR biogenesis. These inhibitors have the potential to (i) dissect miR mechanisms of action, (ii) discover new drug targets, and (iii) function as new therapeutic agents. Here, we designed Förster resonance energy transfer (FRET)-labeled oligoribonucleotides of the precursor of the oncogenic miR-21 (pre-miR-21) and used them together with a set of aminoglycosides to develop an interbase-FRET assay to detect ligand binding to pre-miRs. Our interbase-FRET assay accurately reports structural changes of the RNA oligonucleotide induced by ligand binding. We demonstrate its application in a rapid, qualitative drug candidate screen by assessing the relative binding affinity between 12 aminoglycoside antibiotics and pre-miR-21. Surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) were used to validate our new FRET method, and the accuracy of our FRET assay was shown to be similar to the established techniques. With its advantages over SPR and ITC owing to its high sensitivity, small sample size, straightforward technique and the possibility for high-throughput expansion, we envision that our solution-based method can be applied in pre-miRNA–target binding studies.

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