Krishnarjuna, B and Ganjiwale, Anjali D and Manjappara, Uma V and Raghothama, S (2011) NMR Structure Implications of Enhanced Efficacy of Obestatin Fragment Analogs. In: International Journal of Peptide Research and Therapeutics, 17 (4). pp. 259-270.
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Obestatin is a more recently discovered hormone that is encoded by the ghrelin gene and produced in the stomach and gut. We report NMR analysis on synthetic Obestatin (OB23), a 23 residue peptide, along with three overlapping fragments of the same in methanol solvent as a first step towards structure activity relationship. Selective substitutions on the promising N-terminal and middle fragments of obestatin have been carried out in order to improve the efficacy and potency. In the N-terminal fragment two peptides were obtained by the replacement of Gly (8) with a-aminoisobutyric acid (Aib, U) and Phe (F5) with Cyclohexylalanine (Cha). In case of the middle fragment both Gly (3) and Gly (8) were replaced with Aib residues. The rationale being, these unusual amino acids could provide protection from immediate degradation and aid structure stabilization. Our previous studies showed that the N-terminal and the middle fragment were unstructured and hence this substitution would directly evaluate the effect of structure on the activity of these fragment analogs. Detailed NMR analysis clearly demonstrates formation of helical secondary structure in all the peptide analogues and provides justification for relative activities reported by our group previously (Nagaraj et al. 2009).
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to Springer.|
|Keywords:||Obestatin;Obestatin fragment analogs;NMR;NOE;Helical structure|
|Department/Centre:||Division of Chemical Sciences > NMR Research Centre (Formerly SIF)|
|Date Deposited:||09 Mar 2012 10:45|
|Last Modified:||09 Mar 2012 10:45|
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