Syntheses of fluorinated sugar amino acid derived α,γ-cyclic tetra- and hexapeptides are reported. The IR, NMR, ESI-MS, CD, and molecular modeling studies of cyclic tetra- and hexapeptides showed C and C symmetric flat oval- and triangular-ring shaped β-strand conformations, respectively, which appear to self-assemble into nanotubes. The α,γ-cyclic hexapeptide (EC = 2.14 μM) is found to be a more efficient ion transporter than α,γ-cyclic tetrapeptide (EC = 14.75 μM). The anion selectivity and recognition of α,γ-cyclic hexapeptide with NO ion is investigated.
Orthanilic acid (2-aminobenzenesulfonic acid, (S)Ant), an aromatic β-amino acid, has been shown to be highly useful in inducing a folded conformation in peptides. When incorporated into peptide sequences (Xaa-(S)Ant-Yaa), this rigid aromatic β-amino acid strongly imparts a reverse-turn conformation to the peptide backbone, featuring robust 11-membered-ring hydrogen-bonding.
Although known for their inferiority as hydrogen-bonding acceptors when compared to amides, esters are often found at the C-terminus of peptides and synthetic oligomers (foldamers), presumably due to the synthetic readiness with which they are obtained using protected peptide coupling, deploying amino acid esters at the C-terminus. When the H-bonding interactions deviate from regularity at the termini, peptide chains tend to "fray apart". However, the individual contributions of C-terminal esters in causing peptide chain end-fraying goes often unnoticed, particularly due to diverse competing effects emanating from large peptide chains. Herein, we describe a striking case of a comparison of the individual contributions of C-terminal ester vs. amide carbonyl as a H-bonding acceptor in the folding of a peptide. A simple two-residue peptide fold has been used as a testing case to demonstrate that amide carbonyl is far superior to ester carbonyl in promoting peptide folding, alienating end-fraying. This finding would have a bearing on the fundamental understanding of the individual contributions of stabilizing/destabilizing non-covalent interactions in peptide folding.
Use of human pancreatic
α-amylase (HPA) inhibitors is one
of the effective antidiabetic strategies to lower postprandial hyperglycemia
via reduction in the dietary starch hydrolysis rate. Many natural
products from plants are being studied for their HPA inhibitory activity.
The present study describes isolation of dehydrodieugenol B (DDEB)
from Ocimum tenuiflorum leaves using
sequential solvent extraction, structure determination by one-dimensional
(1D) and two-dimensional (2D) NMR analyses, and characterization as
an HPA inhibitor using kinetics, binding thermodynamics, and molecular
docking. DDEB uncompetitively inhibited HPA with an IC50 value of 29.6 μM for starch and apparent K
i
′ of 2.49 and Ki
of 47.6 μM for starch and maltopentaose
as substrates, respectively. The circular dichroism (CD) study indicated
structural changes in HPA on inhibitor binding. Isothermal titration
calorimetry (ITC) revealed thermodynamically favorable binding (ΔG of −7.79 kcal mol–1) with a dissociation
constant (K
d) of 1.97 μM and calculated
association constant (K
a) of 0.507 μM.
Molecular docking showed stable HPA–inhibitor binding involving
H-bonds and Pi-alkyl, alkyl–alkyl, and van der Waals (vDW)
interactions. The computational docking results support the noncompetitive
nature of DDEB binding. The present study could be helpful for exploration
of the molecule as a potential antidiabetic drug candidate to control
postprandial hyperglycemia.
Herein, we report on the folding pattern observed in a synthetic peptide featuring two highly mutually dependent, yet strikingly dissimilar, closed networks of hydrogen-bonded rings that work in a cumulative fashion to stabilize the entire folded architecture of the peptide. Structural studies unequivocally suggest that disruption of any one of these mutually-dependent hydrogen-bonded networks is deleterious to the stability of the fully folded conformation of the peptide.
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