caa a22 4500 445326522 CHVBK 20180317142722.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10989-011-9266-8 doi (NATIONALLICENCE)springer-10.1007/s10989-011-9266-8 NMR Structure Implications of Enhanced Efficacy of Obestatin Fragment Analogs [Elektronische Daten] [B. Krishnarjuna, Anjali Ganjiwale, Uma Manjappara, S. Raghothama] 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 α-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). Springer Science+Business Media, LLC, 2011 Obestatin nationallicence Obestatin fragment analogs nationallicence NMR nationallicence NOE nationallicence Helical structure nationallicence Krishnarjuna B. NMR Research Centre, Indian Institute of Science, 560 012, Bangalore, India aut Ganjiwale Anjali NMR Research Centre, Indian Institute of Science, 560 012, Bangalore, India aut Manjappara Uma Department of Protein Chemistry and Technology, Central Food Technological Research Institute, 570 020, Mysore, India aut Raghothama S. NMR Research Centre, Indian Institute of Science, 560 012, Bangalore, India aut International Journal of Peptide Research and Therapeutics Springer Netherlands 17/4(2011-12-01), 259-270 1573-3149 17:4<259 2011 17 10989 https://doi.org/10.1007/s10989-011-9266-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10989-011-9266-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Krishnarjuna B. NMR Research Centre, Indian Institute of Science, 560 012, Bangalore, India aut NATIONALLICENCE 700 1- Ganjiwale Anjali NMR Research Centre, Indian Institute of Science, 560 012, Bangalore, India aut NATIONALLICENCE 700 1- Manjappara Uma Department of Protein Chemistry and Technology, Central Food Technological Research Institute, 570 020, Mysore, India aut NATIONALLICENCE 700 1- Raghothama S. NMR Research Centre, Indian Institute of Science, 560 012, Bangalore, India aut NATIONALLICENCE 773 0- International Journal of Peptide Research and Therapeutics Springer Netherlands 17/4(2011-12-01), 259-270 1573-3149 17:4<259 2011 17 10989 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer