Conformational studies of [Nphe5]SFTI-1 by means of 2D NMR spectroscopy in conjunction with molecular dynamics calculations

• Published in: Journal of molecular structure 2015-11, Vol.1100, p.203-207
• Main Authors: Brzozowski, K., Stawikowski, M., Ślusarz, R., Sikorska, E., Lesner, A., Łęgowska, A., Rolka, K.
• Format: Article
• Language: English
• Subjects: Conformational studies; NMR spectroscopy; Peptomers; SFTI1; Trypsin inhibitor
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2015.05.064

Trypsin inhibitor SFTI-1 is the smallest and the most potent among BBI inhibitors. It is also an interesting object for SAR studies since it is cyclic 14 amino acid molecule which additionally contains disulfide bridge. We showed that elimination of head-to-tail cycliztion did not influence its activity. Moreover peptoid monomers of Nlys and Nphe introduced in the substrate specificity P1 position of monocyclic SFTI-1 preserved trypsin and chymotripsin inhibitory activity respectively and made P1–P1′ bond proteolytically stable. These findings motivated us to perform conformational analysis of [Nphe5]SFTI-1 by means of 2D NMR spectroscopy and molecular dynamics calculations. Obtained structure occurred to be in a good agreement with published structures for wild-type SFTI-1, its monocyclic analog with disulfide bridge only as well as one containing Nlys peptoid monomer in P1 position. [Display omitted] •Application of two dimensional NMR spectroscopy in conformational analysis.•Introduction of a peptoid monomer into the sequence of BBI inhibitor.•Solution conformational equilibrium studies.•Application of the combination of experimental and theoretical methods.•We designed an analog which structure is in a good agreement with the native SFTI-1.