We report 250–800 nm UV-Vis monomeric protein absorption originating from protein backbone–sidechain and sidechain–sidechain charge transfer transitions involving Lys/Glu residues.

Aspects of conformational transitions, folding, and misfolding of peptides and proteins have moved into the center of interest in various domains of research at the interface of chemistry, biology, and medicine because of their impact on neurodegenerative diseases.[1] For example, recent research suggests that conformational transitions of soluble amyloid b precursor molecules into aggregated, b-sheet-type forms play a key role in the deposition of cerebral amyloid plaques

Olfactory receptors, which belong to the family of G-protein-coupled receptors, are found to be ectopically expressed in non-sensory tissues mediating a variety of cellular functions. In this study we detected the olfactory receptor OR51E2 at the transcript and the protein level in human epidermal melanocytes. Stimulation of primary melanocytes with the OR51E2 ligand β-ionone significantly inhibited melanocyte proliferation. Our results further showed that β-ionone stimulates melanogenesis and dendritogenesis. Using RNA silencing and receptor antagonists, we demonstrated that OR51E2 activation elevated cytosolic Ca(2+) and cAMP, which could mediate the observed increase in melanin synthesis. Co-immunocytochemical stainings using a specific OR51E2 antibody revealed subcellular localization of the receptor in early endosomes associated with EEA-1 (early endosome antigen 1). Plasma membrane preparations showed that OR51E2 protein is present at the melanocyte cell surface. Our findings thus suggest that activation of olfactory receptor signaling by external compounds can influence melanocyte homeostasis.

The sequential triggering (Soff --> Son) of O, N-acyl migrations (AcM) by chemical and enzymatic methods (Ti) in peptides containing structure-disrupting switch-elements, S (switch-peptides), offers a novel tool for studying in statu nascendi the onset and inhibition of polypeptide folding and self-assembly as a key process in degenerative diseases.

Diabetes has emerged as a threat to the current world. More than ninety five per cent of all the diabetic population has type 2 diabetes mellitus (T2DM). Aggregates of Amylin hormone, which is co-secreted with insulin from the pancreatic β-cells, inhibit the activities of insulin and glucagon and cause T2DM. Importance of the conformationally restricted peptides for drug design against T2DM has been invigorated by recent FDA approval of Symlin, which is a large conformationally restricted peptide. However, Symlin still has some issues including solubility, oral bioavailability and cost of preparation. Herein, we introduced a novel strategy for conformationally restricted peptide design adopting a minimalistic approach for cost reduction. We have demonstrated efficient inhibition of amyloid formation of Amylin and its disruption by a novel class of conformationally restricted β-sheet breaker hybrid peptidomimetics (BSBHps). We have inserted β, γ and δ -aminobenzoic acid separately into an amyloidogenic peptide sequence, synthesized α/β, α/γ and α/δ hybrid peptidomimetics, respectively. Interestingly, we observed the aggregation inhibitory efficacy of α/β and α/γ BSBHps, but not of α/δ analogues. They also disrupt existing amyloids into non-toxic forms. Results may be useful for newer drug design against T2DM as well as other amyloidoses and understanding amyloidogenesis.