Solution structure of a novel T‐cell adhesion inhibitor derived from the fragment of ICAM‐1 receptor: Cyclo(1,8)‐Cys‐Pro‐Arg‐Gly‐Gly‐Ser‐Val‐Cys

Abstract

This study is aimed at elucidating the structure of a novel T-cell adhesion inhibitor, cyclo(1,8)-CPRGGSVC using one-and two-dimensional 1 H NMR and molecular dynamics (MD) simulation. The peptide is derived from the sequence of its parent peptide cIBR (cyclo(1,12)-PenPRGGSVLVTGC), which is a fragment of intercellular adhesion molecule-1 (ICAM-1). Our previous results show that the cyclo(1,8)-CPRGGSVC peptide binds to the LFA-1 I-domain and inhibits heterotypic T-cell adhesion, presumably by blocking the LFA-1/ICAM-1 interactions. The structure of the peptide was determined using NMR and MD simulation in aqueous solution. Our results indicate that the peptide adopts type-I β-turn conformation at the Pro2-Arg3-Gly4-Gly5 (PRGG) sequence. The β-turn structure at the PRGG motif is well conserved in cIBR peptide and ICAM-1 receptor, which suggests the importance of the PRGG motif for the biological activity of cyclo(1,8)-CPRGGSVC peptide. Meanwhile, the Gly5-Ser6-Val7-Cys8-Cys1 (GSVCC) sequence forms a "turn-like" random coil structure that does not belong to any structured motif. Therefore, cyclo(1,8)-CPRGGSVC peptide has only one structured region at the PRGG sequence, which may play an important role in the binding of the peptide to the LFA-1 I-domain. The conserved β-turn conformation of the PRGG motif in ICAM-1, cIBR, and cyclo(1,8)-CPRGGSVC peptides can potentially be used to design peptidomimetics.

Solution Structure and In Silico Binding of a Cyclic Peptide with Hepatitis B Surface Antigen

“…However, only the trans conformation has a unique turn in its three‐dimensional structure. This distinctive type I β‐turn structure at the Glu2‐Thr3‐Gly4‐Ala5 sequence may contribute to its biological activity . Furthermore, the β‐turn may stabilize the overall conformation of this cyclic peptide, which is more stable than in those reported linear peptides .…”

Novel furan‐containing peptide‐based inhibitors of protein arginine deiminase type IV (PAD4)

“…Strong to medium NOE intensities of dαN ( i , i + 1) showed the connectivity of the residues, yet there was no long‐range NOE cross‐peak ( i , i > 2) for the peptide, again ruling out the possibility that the peptide adopted any α‐helical or β‐strand structures. Alpha‐helices or turns normally have 3 J NH–HCα values in the range of 3–7 Hz, while those for β‐strands are mainly in the range of 7–10 Hz . For the random coil model, the average 3 J NH–HCα is approximately 7 Hz .…”