Crystal Structure Analysis of a Cyclic Peptide Drug: High-speed Diffraction Measurement using HyPix-Arc 150°

Introduction

Middle molecule drugs including cyclic peptides are attracting much attention as post-antibody drugs and are "next-generation drugs" that compensate for the challenges of existing small molecule and biopharmaceutical drugs. However, crystals of high molecular weight compounds such as cyclic peptides tend to be too small and fragile to be measured with conventional X-ray diffractometers. The combination of Rigaku‘s ultrabrilliant X-ray source, Hypix-Arc 150° wide-angle detector, and analysis software makes it possible to perform precise structural analysis of even such small crystals in a short time.

Crystalline phase analysis

Figure 1: Microcrystal (left) and crystal structure (right) of cyclosporin A

Conclusion

With a maximum detection angle of about 150°, HyPix-Arc 150° allows for the collection of diffraction data from low to high angles in a short time. Even for small crystals such as cyclosporin A, a dataset that can be used to judge its absolute configuration were obtained in only two hours of measurement (Figure. 1, Table 1). The shortened measurement time is also effective for crystals that are susceptible to X- ray damage, enabling precise structure analysis while maintaining crystallinity. The HyPix-Arc 150° can reliably handle small and fragile samples, which were difficult to handle in the past.