Capsaicin but not Genistein Influences Modulation of Lipid Parameters by Obestatin in DIO-C57BL/6 Mice

International Journal of Peptide Research and Therapeutics - Capsaicin from chillies and genistein from soya bean have been shown to reduce cholesterol and triglyceride levels effectively. This...     

Fragments of obestatin as modulators of feed intake, circulating lipids, and stored fat

Obestatin, shown to reduce feed intake and gain in body weight in rodents, is a very attractive candidate to be used against obesity. In this study, we aimed to investigate the relationship between the primary structure and activity of obestatin. Also of interest to us is a peptide of minimal length that closely mimics obestatin. Towards the same, we synthesized rodent obestatin and three overlapping fragments spanning residues 1-13, 6-18, and 11-23 of obestatin. These peptides subsequent to purification and characterization were tested upon adult male mice for their ability to reduce feed intake and gain in body weight. The N-terminal peptide (residues 1-13) mimicked obestatin the closest. The middle fragment (residues 6-18) significantly reduced epididymal fat without much altering feed intake or body weight.     

Stereochemistry of Schellman motifs in peptides: Crystal structure of a hexapeptide with a C‐terminus 6 → 1 hydrogen bond

The Schellman motif is a widely observed helix terminating structural motif in proteins, which is generated when the C‐terminus residue adopts a left‐handed helical (α_L) conformation. The resulting hydrogen‐bonding pattern involves the formation of an intramolecular 6 → 1 interaction. This helix terminating motif is readily mimicked in synthetic helical peptides by placing an achiral residue at the penultimate position of the sequence. Thus far, the Schellman motif has been characterized crystallographically only in peptide helices of length 7 residues or greater. The structure of the hexapeptide Boc–Pro–Aib–Gly–Leu–Aib–Leu–OMe in crystals reveal a short helical stretch terminated by a Schellman motif, with the formation of 6 → 1 C‐terminus hydrogen bond. The crystals are in the space group P2₁2₁2₁ with a = 18.155(3) Å, b = 18.864(8) Å, c = 11.834(4) Å, and Z = 4 . The final R₁ and wR₂ values are 7.68 and 14.6%, respectively , for 1524 observed reflections [F_o ≥ 3ς(F_o)]. A 6 → 1 hydrogen bond between Pro(1)CO · · · Leu(6)NH and a 5 → 2 hydrogen bond between Aib(2)CO · · · Aib(5)NH are observed. An analysis of the available oligopeptides having an achiral Aib residue at the penultimate position suggests that chain length and sequence effects may be the other determining factors in formation of Schellman motifs. © 1999 John Wiley & Sons, Inc. Biopoly 50: 13–22, 1999     

Impromptu Effects of Nt8U with Soyasaponins on Obesity-related Lipid Parameters in High Fat Fed C57BL/6 Mice

International Journal of Peptide Research and Therapeutics - Nt8U is a peptide analog of the N-terminal 13 residue fragment of the satiety peptide obestatin with Gly (8) being replaced by...     

Fragment analogs as better mimics of obestatin

Obestatin is a twenty three amino acid peptide produced in the stomach by post translational modification of the preproghrelin gene. Since its discovery in 2005, many studies have shown that obestatin reduces feed intake and gain in body weight in rodents. Studies from our laboratory have shown the N-terminal thirteen residues mimic obestatin the best and residues 6–18 reduce epididymal fat significantly in adult male mice. In this study we have tried to increase the efficacy of these fragments. As an initial step, we have substituted G(8) with α-aminoisobutyricacid(Aib,U) and F(5) with cyclohexylalanine(Cha) in the N-terminal peptide to obtain two modified peptides and modified the middle fragment (residues 6–18) by substituting both the glycine residues at position 3 and 8 with α-aminoisobutyricacid(U). The rationale being, unusual amino acids could protect the peptides from immediate degradation and Aib would also induce secondary structure in these unstructured peptides. The N-terminal fragment with the G(8)U substitution fared the best. It reduced food intake, gain in body weight, levels of cholesterol and triglycerides in the blood, epididymal and perirenal fat in adult male mice similar to that of obestatin. The middle fragment with G(3,8)U double substitution was the second best.     

Evaluating the potential of fluorinated tyrosines as spectroscopic probes of local protein environments: a UV resonance Raman study

Ultraviolet resonance Raman (UVRR) studies designed to test the utility of fluorinated tyrosines as spectroscopic probes of the local environment are presented. Specifically, resonance Raman spectra of 2-fluoro-L-tyrosine and 3-fluoro-L-tyrosine (3-Y(f)) obtained with 229 nm excitation are reported. In contrast to the modest environmental dependence of the tyrosine resonance Raman spectrum, the spectrum of 3-Y(f) is found to be extremely dependent on the hydrogen bonding strength of the surrounding environment. Preliminary ab initio studies suggest that this behavior is due to normal modes having dominant contributions from the C-OH and C-F internal coordinates. Hydrogen bonding to the solvent perturbs the internal coordinate energetics and/or couplings, thereby altering the character of the normal modes and the corresponding transition frequencies and/or intensities. In addition to the solvent studies, 3-Y(f) is site specifically incorporated into the influenza hemagglutinin (HA) 100-107 peptide which binds to the Fv fragment of the 17/9 anti-HA(98-108) peptide antibody. These studies demonstrate that the spectrum of 3-Y(f) can be monitored in the presence of native tyrosine. In summary, the studies presented here demonstrate that 3-Y(f) holds exceptional promise as a probe of the protein environment.