Key charged residues influence the amyloidogenic propensity of the helix-1 region of serum amyloid A.

Increased plasma levels of serum amyloid A (SAA), an acute-phase protein that is secreted in response to inflammation, may lead to the accumulation of amyloid in various organs thereby obstructing their functions. Severe cases can lead to a systemic disorder called AA amyloidosis. Previous studies suggest that the N-terminal helix is the most amyloidogenic region of SAA.

Raman Spectroscopic Discrimination of Estrogens.

Estrogens are a group of steroid compounds found in the human body that are eventually discharged and ultimately end up in sewer effluents. Since these compounds can potentially affect the endocrine system its detection and quantification in sewer water is important. In this study, estrogens such as estrone (E1), estradiol (E2), estriol (E3), and ethynylestradiol (EE2) were discriminated and quantitated using Raman spectroscopy.

Molecular Dynamics Simulations on the Bioactive Molecule of hIAPP22-29 (NFGAILSS) and Rational Drug Design.

This chapter includes information about the structure in equilibrium of the bioactive molecule hIAPP22-29 (NFGAILSS). The experimental structure was derived using X-ray and its 2D NOESY NMR experiments in d -DMSO and d-HFIP solvents. This molecule contains eight of the ten amino acids of the 20-29 region of the human islet amyloid polypeptide (hIAPP) often referred as the "amyloidogenic core.

Conformational Differentiation of α-Cyanohydroxycinnamic Acid Isomers: A Raman Spectroscopic Study.

Two α-cyanohydroxycinnamic acid positional isomers, α-cyano-4-hydroxycinnamic acid (CHCA4) and α-cyano-3-hydroxycinnamic acid (CHCA3), were characterized using Raman spectroscopy. We analyzed the implications of the collected Raman spectral shifts, and verified them through other spectroscopic techniques, to arrive at plausible three dimensional structures of CHCA3 and CHCA4. The positions of these groups were mapped by systematically analyzing the orientation and type of interactions functional groups make in each CHCA isomer.

Difference FTIR Studies of Substrate Distribution in Triosephosphate Isomerase.

Triosephosphate isomerase (TIM) catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde 3-phosphate (GAP), via an enediol(ate) intermediate. Determination of substrate population distribution in the TIM/substrate reaction mixture at equilibrium and characterization of the substrate-enzyme interactions in the Michaelis complex are ongoing efforts toward the understanding of the TIM reaction mechanism. By using isotope-edited difference Fourier transform infrared studies with unlabeled and C-labeled substrates at specific carbon(s), we are able to show that in the reaction mixture at equilibrium the keto DHAP is the dominant species and the populations of aldehyde GAP and enediol(ate) are very low, consistent with the results from previous X-ray structural and C NMR studies.

Peptide Conjugates of Benzene Carboxylic Acids as Agonists and Antagonists of Amylin Aggregation.

Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37 residue peptide hormone that is stored and co-secreted with insulin. hIAPP plays a pivotal role in type 2 diabetes and is the major component of amyloid deposits found in the pancreas of patients afflicted with the disease. The self-assembly of hIAPP and the formation of amyloid is linked to the death of insulin producing β-cells.

Vibrational analysis of α-cyanohydroxycinnamic acid.

In the present study, a comparative Raman vibrational analysis of alpha-cyano-4-hydroxycinnamic acid (4CHCA) and its derivative, alpha-cyano-3-hydroxycinnamic acid (3CHCA), was performed. The Raman spectra of the 4CHCA and 3CHCA in solid form were obtained and analyzed to determine differences between the two structurally similar derivatives. For comparison, the CHCA derivatives cyanocinnamic acid (CCA) and coumaric acid (CA) were also studied.

Aromaticity and amyloid formation: effect of π-electron distribution and aryl substituent geometry on the self-assembly of peptides derived from hIAPP(22-29).

A comprehensive investigation of peptides derived from the 22-29 region of human islet amyloid polypeptide (hIAPP) that contain phenylalanine analogs at position 23 with a variety of electron donating and withdrawing groups, along with heteroaromatic surrogates, has been employed to interrogate how π-electron distribution effects amyloid formation. Kinetic aggregation studies using turbidity measurements indicate that electron rich aromatic ring systems consistently abolish the amyloidogenic propensity of hIAPP(22-29). Electron poor systems modulate the rate of aggregation.