Determination of an unusual secondary structural element in the immunostimulating tetrapeptide rigin in aqueous environments: insights via MD simulations, (1)H NMR and CD spectroscopic studies.

Kumar, Nigam and Kishore, Raghuvansh (2010) Determination of an unusual secondary structural element in the immunostimulating tetrapeptide rigin in aqueous environments: insights via MD simulations, (1)H NMR and CD spectroscopic studies. Journal of peptide science : an official publication of the European Peptide Society, 16 (9). pp. 456-64. ISSN 1099-1387

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Abstract

An immunomodulating tetrapeptide, rigin (H-Gly-Gln-Pro-Arg-OH), has been examined for its secondary structure preferences through combined use of high-temperature unrestrained MD simulations in implicit water and 1D and 2D 1H NMR spectroscopy.The distribution of backbone torsion angles revealed the predominance of trans conformers across the Xaa-Pro peptide bond. The results of MD simulations revealed that of the five predicted families A-E, the predominant families, family A (92 structures), family C (63 structures) and family D (31 structures), could be complemented by extensive 1D and 2D 1H NMR parameters acquired in aqueous PBS solution. A survey of specific inter- and intraresidue NOEs substantiated the predominance of an unusual type VII beta-turn structure, defined by two torsion angles, i.e. psiGln approximately 155 degrees and psiPro approximately -65 degrees across the Gln-Pro segment. The proposed semi-folded kinked topology precluded formation of any intramolecular interaction, i.e. hydrogen bond or electrostatic interaction. Far-UV CD spectral characteristics of rigin in aqueous PBS solution and non-aqueous structure promoting organic solvents, TFE and TMP, revealed its strong solvent dependence. However, in aqueous PBS solution, the presence of a weak negative shoulder at approximately 234 nm could be ascribed to a small population with ordered, semi-folded topology.We propose that the plausible structural attributes may be exploited for design and rigidification of the bioactive conformation of this immunomodulator toward improved immunopharmacological properties.

Item Type:	Article
Additional Information:	Copyright of this article belongs to Wiley
Uncontrolled Keywords:	bioactive peptide; conformational analysis; unusual kinked topology; MD simulations; implicit water; spectroscopic studies
Subjects:	Q Science > QD Chemistry
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	08 Dec 2011 19:00
Last Modified:	08 Dec 2011 19:00
URI:	http://crdd.osdd.net/open/id/eprint/506

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